183:
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24:
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in the presence of sodium acetate (e.g., dissolved in a mixture of methanol and water); the reaction was perceived to proceed via a complexation of a pair of carpacins to the Pd(II) metal via their phenolic anions (as shown in scheme, below right), followed by a classic 8-8' (β-β') oxidative phenolic
648:
The
Chapman approach has been applied in a variety of ways since its original report, varying substrates, oxidants, and other aspects (and so synthesis of carpanone has subsequently been achieved by "quite a few research groups"); the actual mechanism of Pd(II) action is likely more complex than the
649:
original conjecture, and there is evidence that the mechanism, broadly speaking, depends on actual conditions (specific substrate, oxidant, etc.). Various groups, including the laboratories of Steve Ley, Craig
Lindley, and Matthew Shair, have succeeded in extending the Chapman method to
639:
For the elegance of its "one-pot construction of a tetracyclic scaffold with complete stereocontrol of five contiguous stereo centers", the original
Chapman design and synthesis is "ow considered a classic in total synthesis" that "highlights the power of biomimetic synthesis".
470:
Carpanone itself is limited in its pharmacologic and biologic activities, but related analogs arrived at by variations of the Brophy-Chapman approach have shown activities as tool compounds relevant to mammalian exocytosis and vesicular traffic, and provided therapeutic
598:
oxidative coupling–Diels Alder reaction sequence. Note, in the second image in the scheme, the two lines crossing at the top are the two molecules overlapping each other (and do not imply chemical bonds). In this scheme, Pd (II) is shown forming a complex between two
539:(carpacin with the methyl of its methoxy group removed). Though oxidative dimerizations of phenols normally used a 1-electron oxidant, Chapman then followed a precedent involving a 2-electron oxidant and treated desmethylcarpacin with PdCl
653:, i.e., phenolic starting materials on polymeric supports, thus allowing the generation of libraries of carpanone analogs. A hetero-8-8' oxidative coupling system akin to the Chapman approach has been developed that uses IPh(OAC)
815:
Brian C. Goess, Rami N. Hannoush, Lawrence K. Chan, Tomas
Kirchhausen, and Matthew D. Shair, 2006, Synthesis of a 10,000-Membered Library of Molecules Resembling Carpanone and Discovery of Vesicular Traffic Inhibitors,
576:. The carpanone is produced in yields of ≈50% by the original method, and in yields >90% in modern variants (see below). The synthesis of a single diastereomer was confirmed in the original Chapman work, using
748:
F. Liron, F. Fontana, J.-O. Zirimwabagabo, G. Prestat, J. Rajabi, C. La Rosa & G. Poli, 2009, A New Cross-Coupling-Based
Synthesis of Carpanone, Org. Lett., 11(19):4378–4381, DOI: 10.1021/ol9017326, see
399:
with a 9-carbon framework, recognized its substructure as being dimerized within the complex carpanone structure, and proposed a hypothesis of how carpacin was converted to carpanone in plant cells:
694:
C.W. Lindsley, C.R. Hopkins & G.A. Sulikowski, 2011, Biomimetic synthesis of lignans, In "Biomimetic
Organic Synthesis" (E. Poupon & B. Nay, Eds.), Weinheim: Wiley-VCH,
347:
most widely known for the remarkably complex way nature prepares it, and the similarly remarkable success that an early chemistry group, that of
Orville L. Chapman, had at
383:), and is notable in its stereochemical complexity, because it contains five contiguous stereogenic centers. The route by which this complex structure is achieved through
317:
206:
InChI=1S/C20H18O6/c1-9-3-11-13(21)5-17-20(25-8-24-17)19(11)18(10(9)2)12-4-15-16(23-7-22-15)6-14(12)26-20/h3-6,9-10,18-19H,7-8H2,1-2H3/t9-,10+,18+,19+,20?/m0/s1
216:
InChI=1/C20H18O6/c1-9-3-11-13(21)5-17-20(25-8-24-17)19(11)18(10(9)2)12-4-15-16(23-7-22-15)6-14(12)26-20/h3-6,9-10,18-19H,7-8H2,1-2H3/t9-,10+,18+,19+,20?/m0/s1
232:
391:
that, almost instantly, take a molecule with little three-dimensionality to the complex final structure. Notably, Brophy and coworkers isolated the simpler
895:
C.W. Lindsley, L.K. Chan, B.C. Goess, R. Joseph & M.D. Shair, 2001, Solid-phase biomimetic synthesis of carpanone-like molecules, J. Am. Chem. Soc.
782:
84:
572:
reaction termed an inverse demand Diels-Alder reaction (see curved arrows in image), which closes the 2 new rings and generates the 5 contiguous
478:
The original
Chapman design and synthesis is considered a classic in total synthesis, and one that highlights the power of biomimetic synthesis.
878:
Per
Lindsley et al., see following, oxidant systems, generally including dioxygen, adventitious or otherwise, include azobisisobutyronitrile, Ag
751:
863:
699:
197:
467:
this proposed biosynthetic route, and achieved the synthesis of carpanone from carpacin in a single "pot", in about 50% yield.
505:), shown below as the starting molecule in the scheme, is acquired in two high-yield steps involving three transformations:
140:
161:
657:, and that allows for preparation of more electron rich homodimers, and for hetero-tetracyclic analogs of carpanone.
324:
915:
Goess, B. C.; Hannoush, R. N.; Chan, L. K.; Kirchhausen, T.; Shair, M. D. J. Am. Chem. Soc. 2006, 128, 5391–5403.
628:
936:
946:
882:
O, M(II) salen systems (M=Co, Mn, Fe), singlet oxygen (hν, Rose Bengal), dibenzoyl peroxide, and IPh(OAC)
632:
603:
of carpacin, then mediating oxidative 8-8' (β-β') phenolic coupling of their alkene tails to generate a
577:
573:
517:
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587:
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799:
G.C. Brophy, J. Mohandas, M. Slaytor, T.R. Watson & L.A. Wilson, 1969, Novel lignans from a
855:
719:
O.L. Chapman, M.R. Engel, J.P. Springer & J.C. Clardy, 1971, Total synthesis of carpanone,
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776:
695:
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Remarkably, within two years, Chapman and coworkers were able to chemically design a route to
104:
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intermediate then underwent a phenolic coupling to generate a dimeric intermediate, which was
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352:
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of the other (shown adjacent in image for clarity), setting the state for a variant of the
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60:
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Baxendale, I. R.; Lee, A.-L.; Ley, S. V. J. Chem. Soc., Perkin Trans. 1 2002, 1850–1857.
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intermediate. A particular conformation of this dimer then places a 4-electron
544:
coupling of the two olefin tails—shown crossing in the image—to give a dimeric
520:
to move the O-allyl group onto the adjacent site on the aromatic ring, and then
918:
Daniels, R. N.; Fadeyi, O. O.; Lindsley, C. W. Org. Lett. 2008, 10, 4097–4100.
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283:
95:
591:
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thermal isomerization of the
Claisen product, to move the terminal olefin (
392:
510:
502:
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23:
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371:
derives its name. The hexacyclic lignan is one of a class of related
340:
459:
reaction to create 2 new rings, to give the final carpanone product.
402:
294:
Except where otherwise noted, data are given for materials in their
582:
561:
499:
401:
375:
isolated from carpano bark as mixtures of equal proportion of the
83:
73:
565:
475:
in antiinfective, antihypertensive, and hepatoprotective areas.
509:
allylation of the phenolic anion generated after treatment of
424:
whose structure was recognized as being dimerized in carpanone
166:
535:
This procedure is one of several that gives the required
527:) into conjugation with the ring (with e.g., potassium
312:
803:
sp. from Bougainville, Tetrahedron Lett. 10:5159-5162.
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128:
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738:
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240:CC1C=C2C3C(C1C)c4cc5c(cc4OC36C(=CC2=O)OCO6)OCO5
59:
838:
836:
834:
832:
823:(16): 5391–5403, DOI: 10.1021/ja056338g, see
367:by Brophy and coworkers, trees from which the
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713:
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8:
513:with potassium carbonate and allyl bromide,
498:in 1971. The required desmethylcarpacin (2-
623:-selective inverse electron-demand hetero-
181:
103:
15:
619:intermediate, followed immediately by an
148:
631:), to close the rings and generates the
429:carpacin underwent loss of a methyl (-CH
666:
237:
202:
177:
781:: CS1 maint: archived copy as title (
774:
209:Key: WTXORUUTAZJKSN-JMAAQRFFSA-N
7:
854:. Weinheim, Germany: VCH. pp.
433:) group from the ring methoxy (-OCH
219:Key: WTXORUUTAZJKSN-JMAAQRFFBX
119:
351:nature's pathway. Carpanone is an
14:
594:into carpanone in one pot, via a
564:of one ring over the 2-electron
302:
267:
22:
437:) group to provide the phenol,
298:(at 25 °C , 100 kPa).
629:Diels–Alder reaction#Mechanism
494:approach published by Chapman
273:
261:
1:
414:, and a more common type of
850:Classics in Total Synthesis
288:354.343 g/mol
963:
451:followed immediately by a
846:; E. J. Sorensen (1996).
651:solid-supported synthesis
379:of its components (i.e.,
339:is a naturally occurring
292:
248:
228:
193:
43:
35:
30:
21:
644:Extensions of the system
355:first isolated from the
826:, accessed 4 June 2014.
705:, accessed 4 June 2014.
790:, accessed 4 June 2014
636:
516:followed by a thermal
425:
586:
578:X-ray crystallography
518:Claisen rearrangement
490:of carpanone was the
405:
389:a series of reactions
661:References and notes
531:-butoxide as base).
365:Bougainville Island
18:
637:
590:transformation of
426:
325:Infobox references
16:
865:978-3-527-29284-4
818:J. Am. Chem. Soc.
721:J. Am. Chem. Soc.
592:desmethylcarpacin
537:desmethylcarpacin
439:desmethylcarpacin
333:Chemical compound
331:
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162:CompTox Dashboard
85:Interactive image
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617:quinone methide
554:quinone methide
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488:total synthesis
484:
482:Total synthesis
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422:phenylpropanoid
397:phenylpropanoid
369:natural product
345:natural product
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766:. Retrieved
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385:biosynthesis
377:"handedness"
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44:Identifiers
36:Other names
726::6697–6698.
625:Diels-Alder
570:Diels-Alder
453:Diels-Alder
249:Properties
926:Categories
899:, 422–423.
801:Cinnamomum
768:2014-06-06
588:Biomimetic
492:biomimetic
486:The first
284:Molar mass
150:G32K37Q6T4
96:ChemSpider
72:3D model (
61:26430-30-8
51:CAS Number
17:Carpanone
556:-type of
387:involves
349:mimicking
337:Carpanone
777:cite web
601:monomers
416:phenolic
410:-methoxy
393:carpacin
105:21864720
38:Cupanone
932:Lignans
511:sesamol
503:sesamol
412:styrene
318:what is
316: (
117:PubChem
942:Enones
862:
702:, see
698:
596:tandem
558:lignan
525:alkene
496:et al.
473:"hits"
455:(4+2)
446:phenol
343:-type
341:lignan
313:verify
310:
233:SMILES
130:291296
31:Names
858:–97.
762:(PDF)
755:(PDF)
613:ortho
609:trans
605:dimer
562:enone
550:ortho
546:trans
500:allyl
465:mimic
444:this
419:plant
408:ortho
363:) of
198:InChI
74:JSmol
860:ISBN
783:link
696:ISBN
621:endo
607:, a
566:enol
529:tert
395:, a
141:UNII
897:122
821:128
787:or
167:EPA
120:CID
928::
856:95
831:^
808:^
779:}}
775:{{
731:^
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580:.
271:18
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886:.
884:2
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771:.
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635:.
615:-
611:-
552:-
548:-
541:2
441:,
435:3
431:3
359:(
308:Y
277:6
274:O
268:H
262:C
169:)
165:(
76:)
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