411:
minimized orientation of the sp center, display one face of an olefin outwards from the ring. Addition of reagents from the outside the olefin face and the ring (peripheral attack) is thus favored, while attack from across the ring on the inward diastereoface is disfavored. Ground state conformations dictate the exposed face of the reactive site of the macrocycle, thus both local and distant stereocontrol elements must be considered. The peripheral attack model holds well for several classes of macrocycles, though relies on the assumption that ground state geometries remain unperturbed in the corresponding
400:
525:
337:
entire structure. For example, in methyl cyclodecane, the ring can be expected to adopt the minimized conformation of boat-chair-boat. The figure below shows the energetic penalty between placing the methyl group at certain sites within the boat-chair-boat structure. Unlike canonical small ring systems, the cyclodecane system with the methyl group placed at the "corners" of the structure exhibits no preference for axial vs. equatorial positioning due to the presence of an unavoidable
452:
621:
143:
505:
cladiell-11-ene-3,6,7-triol makes use of macrocyclic stereocontrol in the dihydroxylation of a trisubstituted olefin. Below is shown the synthetic step controlled by the ground state conformation of the macrocycle, allowing stereoselective dihydroxylation without the usage of an asymmetric reagent. This example of substrate controlled addition is an example of the peripheral attack model in which two centers on the molecule are added two at once in a concerted fashion.
539:
420:
441:
362:
315:
297:
133:
27:
485:
469:
repulsive steric interactions provides the observed product by having the lowest barrier to a transition state for the reaction. Though no external attack by a reagent occurs, this reaction can be thought of similarly to those modeled with peripheral attack; the lowest energy conformation is the most likely to react for a given reaction.
357:
preferences of a molecule. In conjunction with remote substituent effects, local acyclic interactions can also play an important role in determining the outcome of macrocyclic reactions. The conformational flexibility of larger rings potentially allows for a combination of acyclic and macrocyclic stereocontrol to direct reactions.
521:
directed using only ground state conformational preferences and the peripheral attack model. Reacting from the most stable boat-chair-boat conformation, asymmetric epoxidation of the cis-internal olefin can be achieved without using a reagent-controlled epoxidation method or a directed epoxidation with an allylic alcohol.
220:
reaction, providing stereocontrol such as in the synthesis of miyakolide. Computational modeling can predict conformations of medium rings with reasonable accuracy, as Still used molecular mechanics modeling computations to predict ring conformations to determine potential reactivity and stereochemical outcomes.
479:
The lowest energy conformations of macrocycles also influence intramolecular reactions involving transannular bond formation. In the intramolecular
Michael addition sequence below, the ground state conformation minimizes transannular interactions by placing the sp centers at the appropriate vertices,
457:
Conjugate addition to the E-enone below also follows the expected peripheral attack model to yield predominantly trans product. High selectivity in this addition can be attributed to the placement of sp centers such that transannular nonbonded interactions are minimized, while also placing the methyl
446:
However, 10-membered cyclic lactones display significant diastereoselectivity. The proximity of the methyl group to the ester linkage was directly correlated with the diastereomeric ratio of the reaction products, with placement at the 9 position (below) yielding the highest selectivity. In contrast,
336:
These ground-state conformational preferences are useful analogies to more highly functionalized macrocyclic ring systems, where local effects can still be governed to first approximation by energy minimized conformations even though the larger ring size allows more conformational flexibility of the
372:
The stereochemical result of a given reaction on a macrocycle capable of adopting several conformations can be modeled by a Curtin-Hammett scenario. In the diagram below, the two ground state conformations exist in an equilibrium, with some difference in their ground state energies. Conformation B
236:
nonbonded interactions within the ring. Medium rings (8-11 atoms) are the most strained with between 9-13 (kcal/mol) strain energy; analysis of the factors important in considering larger macrocyclic conformations can thus be modeled by looking at medium ring conformations. Conformational analysis
276:
Substitution positional preferences in the ground state conformer of methyl cyclooctane can be approximated using parameters similar to those for smaller rings. In general, the substituents exhibit preferences for equatorial placement, except for the lowest energy structure (pseudo A-value of -0.3
291:
These energetic differences can help rationalize the lowest energy conformations of 8 atom ring structures containing an sp center. In these structures, the chair-boat is the ground state model, with substitution forcing the structure to adopt a conformation such that non-bonded interactions are
468:
Similar to intermolecular reactions, intramolecular reactions can show significant stereoselectivity from the ground state conformation of the molecule. In the intramolecular Diels-Alder reaction depicted below, the lowest energy conformation yields the observed product. The structure minimizing
410:
Macrocyclic rings containing sp centers display a conformational preference for the sp centers to avoid transannular nonbonded interactions by orienting perpendicular to the plan of the ring. Clark W. Still proposed that the ground state conformations of macrocyclic rings, containing the energy
309:
cyclooctanes provided proof of conformational preferences in these medium rings. Significantly, calculated models matched the obtained X-ray data, indicating that computational modeling of these systems could in some cases quite accurately predict conformations. The increased sp character of the
219:
The degree to which a macrocyclic ring is either rigid or floppy depends significantly on the substitution of the ring and the overall size. Significantly, even small conformational preferences, such as those envisioned in floppy macrocycles, can profoundly influence the ground state of a given
520:
The synthesis of (±)-periplanone B is a prominent example of macrocyclic stereocontrol. Periplanone B is a sex pheromone of the
American female cockroach, and has been the target of several synthetic attempts. Significantly, two reactions on the macrocyclic precursor to (±)-periplanone B were
495:
These principles have been applied in multiple natural product targets containing medium and large rings. The syntheses of cladiell-11-ene-3,6,7- triol, (±)-periplanone B, eucannabinolide, and neopeltolide are all significant in their usage of macrocyclic stereocontrol en route to obtaining the
356:
Similar principles guide the lowest energy conformations of larger ring systems. Along with the acyclic stereocontrol principles outlined below, subtle interactions between remote substituents in large rings, analogous to those observed for 8-10 membered rings, can influence the conformational
504:
The cladiellin family of marine natural products possesses interesting molecular architecture, generally containing a 9-membered medium-sized ring. The synthesis of (−)-cladiella-6,11-dien-3-ol allowed access to a variety of other members of the cladiellin family. Notably, the conversion to
570:
Neopeltolide was originally isolated from sponges near the
Jamaican coast and exhibits nanomolar cytoxic activity against several lines of cancer cells. The synthesis of the neopeltolide macrocyclic core displays a hydrogenation controlled by the ground state conformation of the macrocycle.
223:
Reaction classes used in synthesis of natural products under the macrocyclic stereocontrol model for obtaining a desired stereochemistry include: hydrogenations such as in neopeltolide and (±)-methynolide, epoxidations such as in (±)-periplanone B and lonomycin A, hydroborations such as in
425:
Early investigations of macrocyclic stereocontrol studied the alkylation of 8-membered cyclic ketones with varying substitution. In the example below, alkylation of 2-methylcyclooctanone occurred to yield the predominantly trans product. Proceeding from the lowest energy conformation of
534:
of the ketone was achieved, and can be modeled by peripheral attack of the sulfur ylide on the carbonyl group in a
Johnson-Corey-Chaykovsky reaction to yield the protected form of (±)-periplanone B. Deprotection of the alcohol followed by oxidation yielded the desired natural product.
463:
431:
326:
447:
when the methyl group was placed at the 7 position, a 1:1 mixture of diastereomers was obtained. Placement of the methyl group at the 9-position in the axial position yields the most stable ground state conformation of the 10-membered ring leading to high diastereoselectivity.
277:
kcal/mol in figure below) in which axial substitution is favored. The "pseudo A-value" is best treated as the approximate energy difference between placing the methyl substituent in the equatorial or axial positions. The most energetically unfavorable interaction involves
246:
377:
to its transition state in a hypothetical reaction, thus the product formed is predominantly product B (P B) arising from conformation B via transition state B (TS B). The inherent preference of a ring to exist in one conformation over another provides a tool for
286:
332:
Similar to cyclooctane, a cyclodecane ring exhibits several conformations with two lower energy conformations. The boat-chair-boat conformation is energetically minimized, while the chair-chair-chair conformation has significant eclipsing interactions.
474:
560:
390:, the free energy difference, which can, at some level, be estimated from conformational analysis. The free energy difference between the two transition states of each conformation on its path to product formation is given by ΔΔG. The value of ΔG
576:
426:
2-methylcycloctanone, peripheral attack is observed from either one of the low energy (energetic difference of 0.5 (kcal/mol)) enolate conformations, resulting in a trans product from either of the two depicted transition state conformations.
555:. Significantly, the synthesis of eucannabinolide relied on the usage of molecular mechanics (MM2) computational modeling to predict the lowest energy conformation of the macrocycle to design substrate-controlled stereochemical reactions.
510:
394:
between not just one, but many accessible conformations is the underlying energetic impetus for reactions occurring from the most stable ground state conformation and is the crux of the peripheral attack model outlined below.
215:
in the late 1970s and 1980s challenged this assumption, while several others found crystallographic data and NMR data that suggested macrocyclic rings were not the floppy, conformationally ill-defined species many assumed.
99:
macrocycles. The central challenge to macrocyclization is that ring-closing reactions do not favor the formation of large rings. Instead, small rings or polymers tend to form. This kinetic problem can be addressed by using
292:
minimized from the parent structure. From the cyclooctene figure below, it can be observed that one face is more exposed than the other, foreshadowing a discussion of privileged attack angles (see peripheral attack).
550:
In the synthesis of the cytotoxic germacranolide sesquiterpene eucannabinolide, Still demonstrates the application of the peripheral attack model to the reduction of a ketone to set a new stereocenter using
272:
interactions (shown in blue), as well as torsional strain. The chair-chair conformation is the second most abundant conformation at room temperature, with a ratio of 96:4 chair-boat:chair-chair observed.
341:
interaction in both conformations. Significantly more intense interactions develop when the methyl group is placed in the axial position at other sites in the boat-chair-boat conformation.
458:
substitution in the more energetically favorable position for cyclodecane rings. This ground state conformation heavily biases conjugate addition to the less hindered diastereoface.
224:
9-dihydroerythronolide B, enolate alkylations such as in (±)-3-deoxyrosaranolide, dihydroxylations such as in cladiell-11-ene-3,6,7-triol, and reductions such as in eucannabinolide.
115:
are often generated in the presence of an alkali metal cation, which organizes the condensing components by complexation. An illustrative macrocyclization is the synthesis of (−)-
346:
78:: Cyclic macromolecule or a macromolecular cyclic portion of a macromolecule. Note 1: A cyclic macromolecule has no end-groups but may nevertheless be regarded as a chain.
68:
1629:
Marsault, Eric; Peterson, Mark L. (2011-04-14). "Macrocycles Are Great Cycles: Applications, Opportunities, and
Challenges of Synthetic Macrocycles in Drug Discovery".
972:
Kamat, V.P.; Hagiwara, H.; Katsumi, T.; Hoshi, T.; Suzuki, T.; Ando, M. (2000). "Ring
Closing Metathesis Directed Synthesis of (R)-(−)-Muscone from (+)-Citronellal".
81:
Note 2: In the literature, the term macrocycle is sometimes used for molecules of low relative molecular mass that would not be considered macromolecules.
749:
Zhichang Liu; Siva
Krishna Mohan Nalluria; J. Fraser Stoddart (2017). "Surveying macrocyclic chemistry: from flexible crown ethers to rigid cyclophanes".
111:. Templates are ions, molecules, surfaces etc. that bind and pre-organize compounds, guiding them toward formation of a particular ring size. The
188:
rings is well established in organic chemistry, in large part due to the axial/equatorial preferential positioning of substituents on the ring.
237:
of odd-membered rings suggests they tend to reside in less symmetrical forms with smaller energy differences between stable conformations.
1018:
1068:
J. D. Dunitz. Perspectives in
Structural Chemistry (Edited by J. D. Dunitz and J. A. Ibers), Vol. 2, pp. l-70; Wiley, New York (1968)
928:
821:
911:
Gerbeleu, Nicolai V.; Arion, Vladimir B.; Burgess, John (2007). Nicolai V. Gerbeleu; Vladimir B. Arion; John
Burgess (eds.).
386:
are significant considerations in this scenario. The preference for one conformation over another can be characterized by ΔG
785:
382:
control of reactions by biasing the ring into a given configuration in the ground state. The energy differences, ΔΔG and ΔG
1561:
Choi, Kihang; Hamilton, Andrew D. (2003). "Macrocyclic anion receptors based on directed hydrogen bonding interactions".
613:
across hydrophobic membranes and solvents. The macrocycle envelops the ion with a hydrophobic sheath, which facilitates
232:
Macrocycles can access a number of stable conformations, with preferences to reside in those that minimize the number of
345:
1713:
Iyoda, Masahiko; Yamakawa, Jun; Rahman, M. Jalilur (2011-11-04). "Conjugated
Macrocycles: Concepts and Applications".
436:
Unlike the cyclooctanone case, alkylation of 2-cyclodecanone rings does not display significant diastereoselectivity.
862:"Macrocyclization Reactions: The Importance of Conformational, Configurational, and Template-Induced Preorganization"
203:
Early assumptions towards macrocycles in synthetic chemistry considered them far too floppy to provide any degree of
1676:
Chambron, J-C.; Dietrich-Buchecker, C.; Hemmert, C.; Khemiss, A-K.; Mitchell, D.; Sauvage, J-P.; Weiss, J. (1990).
668:
132:
175:
399:
614:
171:
124:
101:
787:
IUPAC. Compendium of Polymer Terminology and Nomenclature, IUPAC Recommendations 2008 (the "Purple Book")
974:
524:
278:
1759:
310:
cyclopropane rings favor them to be placed similarly such that they relieve non-bonded interactions.
146:
306:
1507:"Classics in Stereoselective Synthesis". Carreira, Erick M.; Kvaerno, Lisbet. Weinheim: Wiley-VCH,
839:"Cyclic and Macrocyclic OrganicCompounds – a Personal Review in Honor of Professor Leopold Ružička"
620:
338:
538:
451:
1701:
680:
663:
268:. Cyclooctane prefers to reside in a chair-boat conformation, minimizing the number of eclipsing
261:
17:
784:
R. G. Jones; J. Kahovec; R. Stepto; E. S. Wilks; M. Hess; T. Kitayama; W. V. Metanomski (2008).
257:
142:
1677:
462:
265:
1738:
1730:
1654:
1646:
1611:
1148:
1014:
950:
924:
893:
817:
766:
731:
374:
193:
181:
108:
256:. Spectroscopic methods have determined that cyclooctane possesses three main conformations:
1722:
1693:
1685:
1638:
1601:
1570:
1138:
1130:
1006:
983:
946:"Macrocyclic Polyethers: Dibenzo-18-Crown-6 Polyether and Dicyclohexyl-18-Crown-6 Polyether"
916:
883:
873:
860:
Vicente Martí-Centelles; Mrituanjay D. Pandey; M. Isabel Burguete; Santiago V. Luis (2015).
809:
758:
721:
713:
430:
412:
325:
45:
419:
606:. These rings arise from multistep biosynthetic processes that also feature macrocycles.
440:
379:
245:
159:
314:
296:
200:
elements providing enough conformational influence to direct the outcome of a reaction.
1143:
1118:
656:
591:
484:
212:
208:
204:
167:
1574:
1117:
Kamenik, Anna S.; Lessel, Uta; Fuchs, Julian E.; Fox, Thomas; Liedl, Klaus R. (2018).
987:
726:
701:
361:
1753:
610:
1705:
285:
1119:"Peptidic Macrocycles - Conformational Sampling and Thermodynamic Characterization"
233:
61:
30:
16:
For the molecular effect giving increased stability to coordination complexes, see
1010:
1590:"Design, Properties and Recent Application of Macrocycles in Medicinal Chemistry"
717:
192:
stereocontrol models the substitution and reactions of medium and large rings in
1381:
Anet, F.A.L.; St. Jacques, M.; Henrichs, P.M.; Cheng, A.K.; Krane, J.; Wong, L.
945:
878:
861:
531:
253:
197:
185:
120:
112:
49:
473:
625:
559:
104:, whereby intramolecular processes are favored relative to polymerizations.
53:
1734:
1650:
1134:
1697:
1606:
1589:
595:
587:
575:
96:
57:
34:
26:
1742:
1726:
1658:
1615:
1152:
897:
770:
920:
813:
735:
651:
646:
641:
594:. Many metallocofactors are bound to macrocyclic ligands, which include
888:
762:
632:
Macrocycles are often bioactive and could be useful for drug delivery.
603:
509:
373:
is lower in energy than conformation A, and while possessing a similar
116:
1642:
537:
599:
269:
806:
Modern Supramolecular Chemistry: Strategies for Macrocycle Synthesis
586:
One important application are the many macrocyclic antibiotics, the
804:
François Diederich; Peter J. Stang; Rik R. Tykwinski, eds. (2008).
252:
Conformational analysis of medium rings begins with examination of
1275:
Mulzer, J.; Kirstein, H.M.; Buschmann, J.; Lehmann, C.; Luger, P.
619:
302:
141:
838:
281:
at the vertex of the boat portion of the ring (6.1 kcal/mol).
702:"Chemistry and Biology of the Polyene Macrolide Antibiotics"
523:
324:
244:
131:
1165:
Evans, D. A.; Ripin, D.H.B.; Halstead, D.P.; Campos, K. R.
37:
antibiotic, is one of many naturally occurring macrocycles.
64:. Macrocycles describe a large, mature area of chemistry.
1540:
Scheerer, J.R.; Lawrence, J.F.; Wang, G.C.; Evans, D.A.
1255:
Evans, D.A.; Ratz, A.M.; Huff, B.E.; and Sheppard, G.S.
1001:
Paul R. Ortiz de Montellano (2008). "Hemes in Biology".
48:
of twelve or more atoms. Classical examples include the
91:
The formation of macrocycles by ring-closure is called
44:
are often described as molecules and ions containing a
1678:"Interlacing molecular threads on transition metals"
1344:Still, W.C.; Murata, S.; Revial, G.; Yoshihara, K.
1112:
1110:
843:Cyclic and Macrocyclic Organic Compounds, Kem. Ind
1460:
1458:
73:
95:. Pioneering work was reported for studies on
1503:
1501:
8:
1441:Schreiber, S. L.; Smith, D. B.; Schulte, G.
1321:Kim, H.; Lee, H.; Kim, J.; Kim, S.; Kim, D.
1123:Journal of Chemical Information and Modeling
624:The potassium (K) complex of the macrocycle
480:while also minimizing diaxial interactions.
1364:Eliel, E.L., Wilen, S.H. and Mander, L.S. (
913:Template Synthesis of Macrocyclic Compounds
609:Macrocycles often bind ions and facilitate
1594:CHIMIA International Journal for Chemistry
1340:
1338:
1294:
1292:
1231:
1229:
1227:
1225:
211:control in a reaction. The experiments of
174:chemical reaction that is governed by the
166:refers to the directed outcome of a given
1605:
1208:Vedejs, E.; Buchanan, R.A.; Watanabe, Y.
1142:
1077:Anet, F. A. L.; Degen, P. J.; Yavari. I.
887:
877:
725:
368:Reactivity and conformational preferences
107:Some macrocyclizations are favored using
1097:Casarini, D.; Lunazzi, L.; Mazzanti, A.
1044:
1042:
1040:
1038:
1036:
1034:
1032:
1030:
1005:. John Wiley & Sons. pp. 1–10.
123:. The 15-membered ring is generated by
25:
1715:Angewandte Chemie International Edition
692:
149:, biosynthetic precursor to porphyrins.
1317:
1315:
1003:Wiley Encyclopedia of Chemical Biology
1370:Stereochemistry of Organic Compounds,
1184:
1182:
7:
1421:Pawar, D.M.; Moody, E.M.; Noe, E.A.
1372:John Wiley and Sons, Inc., New York.
23:Molecule with a large ring structure
14:
793:. RSC Publishing, Cambridge, UK.
574:
558:
508:
483:
472:
461:
450:
439:
429:
418:
398:
360:
344:
313:
295:
284:
491:Prominent examples in synthesis
1631:Journal of Medicinal Chemistry
1588:Ermert, Philipp (2017-10-25).
1563:Coordination Chemistry Reviews
1:
1575:10.1016/s0010-8545(02)00305-3
1401:Petasis, N. A.; Patane, M.A.
1011:10.1002/9780470048672.wecb221
988:10.1016/S0040-4020(00)00333-1
944:Pedersen, Charles J. (1988).
718:10.1128/br.37.2.166-196.1973
700:Hamilton-Miller, JM (1973).
496:desired structural targets.
178:preference of a macrocycle.
136:Synthesis of muscone via RCM
1048:Still, W. C.; Galynker, I.
879:10.1021/acs.chemrev.5b00056
582:Occurrence and applications
500:Cladiell-11-ene-3,6,7-triol
406:The peripheral attack model
1776:
1298:Still, W.C.; Novack, V.J.
1188:Tu, W.; Floreancig, P. E.
960:, vol. 6, p. 395
228:Conformational preferences
15:
669:Macrocyclic stereocontrol
164:macrocyclic stereocontrol
1135:10.1021/acs.jcim.8b00097
751:Chemical Society Reviews
1698:10.1351/pac199062061027
1607:10.2533/chimia.2017.678
706:Bacteriological Reviews
125:ring-closing metathesis
102:high-dilution reactions
1727:10.1002/anie.201006198
629:
542:
528:
329:
249:
150:
137:
83:
38:
1190:Angew. Chem. Int. Ed.
921:10.1002/9783527613809
814:10.1002/9783527621484
623:
541:
527:
328:
248:
145:
135:
29:
147:Uroporphyrinogen III
1721:(45): 10522–10553.
352:Larger ring systems
1520:Deslongchamps, P.
1464:Deslongchamps, P.
1099:Eur. J. Org. Chem.
837:H. Höcker (2009).
763:10.1039/c7cs00185a
681:Macrocyclic ligand
664:Effective molarity
630:
543:
529:
330:
279:axial substitution
250:
151:
138:
109:template reactions
39:
18:Macrocyclic effect
1643:10.1021/jm1012374
1542:J. Am. Chem. Soc.
1522:J. Am. Chem. Soc.
1346:J. Am. Chem. Soc.
1323:J. Am. Chem. Soc.
1300:J. Am. Chem. Soc.
1277:J. Am. Chem. Soc.
1257:J. Am. Chem. Soc.
1237:J. Am. Chem. Soc.
1210:J. Am. Chem. Soc.
1167:J. Am. Chem. Soc.
982:(26): 4397–4403.
958:Collected Volumes
951:Organic Syntheses
872:(16): 8736–8834.
516:(±)-Periplanone B
415:of the reaction.
194:organic chemistry
1767:
1746:
1709:
1686:Pure Appl. Chem.
1682:
1663:
1662:
1637:(7): 1961–2004.
1626:
1620:
1619:
1609:
1585:
1579:
1578:
1569:(1–2): 101–110.
1558:
1552:
1538:
1532:
1518:
1512:
1505:
1496:
1482:
1476:
1466:Pure Appl. Chem.
1462:
1453:
1439:
1433:
1419:
1413:
1399:
1393:
1379:
1373:
1362:
1356:
1342:
1333:
1319:
1310:
1296:
1287:
1273:
1267:
1253:
1247:
1233:
1220:
1206:
1200:
1186:
1177:
1163:
1157:
1156:
1146:
1114:
1105:
1095:
1089:
1075:
1069:
1066:
1060:
1046:
1025:
1024:
998:
992:
991:
969:
963:
961:
954:
941:
935:
934:
908:
902:
901:
891:
881:
857:
851:
850:
834:
828:
827:
801:
795:
794:
792:
781:
775:
774:
757:(9): 2459–2478.
746:
740:
739:
729:
697:
578:
562:
512:
487:
476:
465:
454:
443:
433:
422:
413:transition state
402:
364:
348:
317:
299:
288:
1775:
1774:
1770:
1769:
1768:
1766:
1765:
1764:
1750:
1749:
1712:
1680:
1675:
1672:
1670:Further reading
1667:
1666:
1628:
1627:
1623:
1600:(10): 678–702.
1587:
1586:
1582:
1560:
1559:
1555:
1539:
1535:
1519:
1515:
1506:
1499:
1483:
1479:
1463:
1456:
1440:
1436:
1420:
1416:
1400:
1396:
1380:
1376:
1363:
1359:
1343:
1336:
1320:
1313:
1297:
1290:
1274:
1270:
1254:
1250:
1234:
1223:
1207:
1203:
1187:
1180:
1164:
1160:
1116:
1115:
1108:
1096:
1092:
1076:
1072:
1067:
1063:
1047:
1028:
1021:
1000:
999:
995:
971:
970:
966:
956:
943:
942:
938:
931:
910:
909:
905:
859:
858:
854:
836:
835:
831:
824:
803:
802:
798:
790:
783:
782:
778:
748:
747:
743:
699:
698:
694:
689:
677:
638:
584:
579:
568:
563:
554:
548:
546:Eucannabinolide
518:
513:
502:
493:
488:
477:
466:
455:
444:
434:
423:
408:
403:
393:
389:
385:
380:stereoselective
370:
365:
354:
349:
323:
318:
300:
289:
243:
230:
160:stereochemistry
156:
93:macrocylization
89:
84:
72:
24:
21:
12:
11:
5:
1773:
1771:
1763:
1762:
1752:
1751:
1748:
1747:
1710:
1692:(6): 1027–34.
1671:
1668:
1665:
1664:
1621:
1580:
1553:
1533:
1531:, 13989-13995.
1513:
1497:
1484:Seeman, J. I.
1477:
1454:
1434:
1414:
1394:
1374:
1357:
1334:
1332:, 15851-15855.
1311:
1288:
1268:
1248:
1221:
1201:
1178:
1158:
1129:(5): 982–992.
1106:
1090:
1070:
1061:
1026:
1020:978-0470048672
1019:
993:
964:
936:
929:
903:
852:
829:
822:
796:
776:
741:
712:(2): 166–196.
691:
690:
688:
685:
684:
683:
676:
673:
672:
671:
666:
660:
659:
657:Molecular knot
654:
649:
644:
637:
634:
615:phase transfer
592:clarithromycin
583:
580:
573:
567:
564:
557:
552:
547:
544:
517:
514:
507:
501:
498:
492:
489:
482:
471:
460:
449:
438:
428:
417:
407:
404:
397:
391:
387:
383:
375:energy barrier
369:
366:
359:
353:
350:
343:
322:
319:
312:
307:functionalized
294:
283:
242:
239:
229:
226:
213:W. Clark Still
205:stereochemical
196:, with remote
176:conformational
172:intramolecular
168:intermolecular
155:
152:
140:
139:
88:
85:
67:
66:
22:
13:
10:
9:
6:
4:
3:
2:
1772:
1761:
1758:
1757:
1755:
1744:
1740:
1736:
1732:
1728:
1724:
1720:
1716:
1711:
1707:
1703:
1699:
1695:
1691:
1688:
1687:
1679:
1674:
1673:
1669:
1660:
1656:
1652:
1648:
1644:
1640:
1636:
1632:
1625:
1622:
1617:
1613:
1608:
1603:
1599:
1595:
1591:
1584:
1581:
1576:
1572:
1568:
1564:
1557:
1554:
1550:
1546:
1543:
1537:
1534:
1530:
1526:
1523:
1517:
1514:
1510:
1504:
1502:
1498:
1494:
1490:
1487:
1481:
1478:
1474:
1470:
1467:
1461:
1459:
1455:
1451:
1447:
1444:
1443:J. Org. Chem.
1438:
1435:
1431:
1427:
1424:
1423:J. Org. Chem.
1418:
1415:
1411:
1407:
1404:
1398:
1395:
1391:
1387:
1384:
1378:
1375:
1371:
1367:
1361:
1358:
1354:
1350:
1347:
1341:
1339:
1335:
1331:
1327:
1324:
1318:
1316:
1312:
1308:
1304:
1301:
1295:
1293:
1289:
1285:
1281:
1278:
1272:
1269:
1265:
1261:
1258:
1252:
1249:
1245:
1241:
1238:
1232:
1230:
1228:
1226:
1222:
1218:
1214:
1211:
1205:
1202:
1198:
1194:
1191:
1185:
1183:
1179:
1175:
1171:
1168:
1162:
1159:
1154:
1150:
1145:
1140:
1136:
1132:
1128:
1124:
1120:
1113:
1111:
1107:
1103:
1100:
1094:
1091:
1087:
1083:
1080:
1079:J. Org. Chem.
1074:
1071:
1065:
1062:
1058:
1054:
1051:
1045:
1043:
1041:
1039:
1037:
1035:
1033:
1031:
1027:
1022:
1016:
1012:
1008:
1004:
997:
994:
989:
985:
981:
977:
976:
968:
965:
959:
953:
952:
947:
940:
937:
932:
930:9783527613809
926:
922:
918:
915:. Wiley-VCH.
914:
907:
904:
899:
895:
890:
885:
880:
875:
871:
867:
863:
856:
853:
848:
844:
840:
833:
830:
825:
823:9783527621484
819:
815:
811:
808:. Wiley-VCH.
807:
800:
797:
789:
788:
780:
777:
772:
768:
764:
760:
756:
752:
745:
742:
737:
733:
728:
723:
719:
715:
711:
707:
703:
696:
693:
686:
682:
679:
678:
674:
670:
667:
665:
662:
661:
658:
655:
653:
650:
648:
645:
643:
640:
639:
635:
633:
627:
622:
618:
617:properties.
616:
612:
611:ion transport
607:
605:
601:
597:
593:
589:
581:
577:
572:
565:
561:
556:
545:
540:
536:
533:
526:
522:
515:
511:
506:
499:
497:
490:
486:
481:
475:
470:
464:
459:
453:
448:
442:
437:
432:
427:
421:
416:
414:
405:
401:
396:
381:
376:
367:
363:
358:
351:
347:
342:
340:
339:gauche-butane
334:
327:
320:
316:
311:
308:
304:
298:
293:
287:
282:
280:
274:
271:
267:
263:
259:
255:
247:
240:
238:
235:
227:
225:
221:
217:
214:
210:
209:regiochemical
206:
201:
199:
195:
191:
187:
183:
182:Stereocontrol
179:
177:
173:
169:
165:
161:
154:Stereocontrol
153:
148:
144:
134:
130:
129:
128:
126:
122:
118:
114:
110:
105:
103:
98:
94:
86:
82:
79:
77:
70:
65:
63:
62:cyclodextrins
59:
55:
51:
47:
43:
36:
32:
28:
19:
1718:
1714:
1689:
1684:
1634:
1630:
1624:
1597:
1593:
1583:
1566:
1562:
1556:
1551:, 8968-8969.
1548:
1544:
1541:
1536:
1528:
1524:
1521:
1516:
1508:
1492:
1488:
1485:
1480:
1475:, 1831-1847.
1472:
1468:
1465:
1452:, 5994-5996.
1449:
1445:
1442:
1437:
1432:, 4586-4589.
1429:
1425:
1422:
1417:
1412:, 5757-5821.
1409:
1405:
1402:
1397:
1392:, 1629-1637.
1389:
1385:
1382:
1377:
1369:
1365:
1360:
1352:
1348:
1345:
1329:
1325:
1322:
1309:, 1148-1149.
1306:
1302:
1299:
1283:
1279:
1276:
1271:
1266:, 3448-3467.
1263:
1259:
1256:
1251:
1246:, 2493-2495.
1243:
1239:
1236:
1235:Still, W.C.
1219:, 8430-8438.
1216:
1212:
1209:
1204:
1199:, 4567-4571.
1196:
1192:
1189:
1176:, 6816-6826.
1173:
1169:
1166:
1161:
1126:
1122:
1104:, 2035-2056.
1101:
1098:
1093:
1088:, 3021-3023.
1085:
1081:
1078:
1073:
1064:
1059:, 3981-3996.
1056:
1052:
1049:
1002:
996:
979:
973:
967:
957:
949:
939:
912:
906:
889:10234/154905
869:
865:
855:
846:
842:
832:
805:
799:
786:
779:
754:
750:
744:
709:
705:
695:
636:Subdivisions
631:
608:
585:
569:
566:Neopeltolide
549:
530:
519:
503:
494:
478:
467:
456:
445:
435:
424:
409:
371:
355:
335:
331:
305:analysis of
301:
290:
275:
251:
234:transannular
231:
222:
218:
202:
189:
180:
163:
157:
113:crown ethers
106:
92:
90:
80:
75:
74:
50:crown ethers
41:
40:
31:Erythromycin
1760:Macrocycles
1403:Tetrahedron
1383:Tetrahedron
1050:Tetrahedron
975:Tetrahedron
532:Epoxidation
321:Cyclodecane
262:chair-chair
254:cyclooctane
241:Cyclooctane
198:stereogenic
190:Macrocyclic
186:cyclohexane
121:citronellal
54:calixarenes
42:Macrocycles
1511:. pp 1-16.
1486:Chem. Rev.
1355:, 625-627.
1286:, 910-923.
687:References
626:18-crown-6
596:porphyrins
588:macrolides
258:chair-boat
76:Macrocycle
71:definition
58:porphyrins
1735:1521-3773
1651:0022-2623
1495:, 83-134.
866:Chem. Rev
266:boat-boat
119:from (+)-
97:terpenoid
87:Synthesis
35:macrolide
1754:Category
1743:21960431
1706:21741762
1659:21381769
1616:29070413
1153:29652495
898:26248133
849:: 73–80.
771:28462968
675:See also
652:Catenane
647:Rotaxane
642:Cryptand
604:chlorins
1144:5974701
736:4578757
600:corrins
590:, e.g.
117:muscone
1741:
1733:
1704:
1657:
1649:
1614:
1151:
1141:
1017:
927:
896:
820:
769:
734:
727:413810
724:
602:, and
270:ethane
264:, and
60:, and
1702:S2CID
1681:(PDF)
791:(PDF)
303:X-ray
69:IUPAC
1739:PMID
1731:ISSN
1655:PMID
1647:ISSN
1612:PMID
1545:2007
1525:2008
1509:2009
1489:1983
1469:1992
1446:1989
1426:1999
1406:1992
1386:1974
1366:1994
1349:1983
1326:2006
1303:1984
1280:1991
1260:1995
1240:1979
1213:1989
1193:2009
1170:1999
1149:PMID
1102:2010
1082:1978
1053:1981
1015:ISBN
925:ISBN
894:PMID
818:ISBN
767:PMID
732:PMID
551:NaBH
184:for
46:ring
33:, a
1723:doi
1694:doi
1639:doi
1602:doi
1571:doi
1567:240
1549:129
1529:130
1353:105
1330:128
1307:106
1284:113
1264:117
1244:101
1217:111
1174:121
1139:PMC
1131:doi
1007:doi
984:doi
917:doi
884:hdl
874:doi
870:115
810:doi
759:doi
722:PMC
714:doi
207:or
170:or
158:In
1756::
1737:.
1729:.
1719:50
1717:.
1700:.
1690:62
1683:.
1653:.
1645:.
1635:54
1633:.
1610:.
1598:71
1596:.
1592:.
1565:.
1547:,
1500:^
1493:83
1491:,
1473:64
1471:,
1457:^
1450:54
1448:,
1430:64
1428:,
1410:48
1408:,
1390:30
1388:,
1368:)
1351:,
1337:^
1328:,
1314:^
1305:,
1291:^
1282:,
1262:,
1242:,
1224:^
1215:,
1197:48
1195:,
1181:^
1172:,
1147:.
1137:.
1127:58
1125:.
1121:.
1109:^
1086:43
1084:,
1057:37
1055:,
1029:^
1013:.
980:56
978:.
955:;
948:.
923:.
892:.
882:.
868:.
864:.
847:58
845:.
841:.
816:.
765:.
755:46
753:.
730:.
720:.
710:37
708:.
704:.
598:,
260:,
162:,
127:.
56:,
52:,
1745:.
1725::
1708:.
1696::
1661:.
1641::
1618:.
1604::
1577:.
1573::
1527:,
1155:.
1133::
1023:.
1009::
990:.
986::
962:.
933:.
919::
900:.
886::
876::
826:.
812::
773:.
761::
738:.
716::
628:.
553:4
392:0
388:0
384:0
20:.
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
