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InChI=1S/C45H48O21/c1-6-8-42(60)40(58)32(54)24(46)14-11-12-10-13-16(25(47)15(12)38(56)44(14,42)61)26(48)20(37(65-5)34(13)63-3)19-27(49)17-18(30(52)36(19)64-4)28(50)21-22(29(17)51)39(57)45(62)23-31(53)33(55)41(59)43(45,9-7-2)66-35(21)23/h10,14,23-24,31-33,35,40-41,46-48,50-51,53-55,58-62H,6-9,11H2,1-5H3/t14-,23+,24+,31+,32-,33-,35+,40+,41+,42+,43+,44-,45-/m1/s1
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The biosynthesis of hibarimicinone was initially hypothesized to be produced from a polyketide synthase. Through 13C-labelling and blocked mutants of the TP-A0121 strain, Oki et al. demonstrated that hibarimicinone is produced by an oxidative coupling of two tetracyclic polyketides, which undergo an
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derived two carbon ketide unit. The KS/CLF binds to the starting butyryl-CoA, freeing the ACP domain to bind to another malonate group from malonyl-CoA. Thioester exchange occurs between the KS/CLF and the ACP; the cycle then repeats nine more times to produce the full carbon chain
319:, with steric hindrance imposed by the four ortho substituents. The absolute configuration around the axis was elucidated by Romaine et al., utilizing a C2-symmetric shunt metabolite HMP-Y6, a glycosylated structural analogue of hibarimicinone, in tandem with
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oxidative cyclization to generate the ether ring. The hibarimicinone monomer is formed initially by a Type II polyketide synthase. The 22 carbon chain is initiated by butyryl-CoA and its
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backbone, which are now known as the hibarimicins. Hibarimicinone and its derivatives were initially extracted for their potential inhibitory properties of various
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315:(PTK). The atropisomerism that the hibarimicin family possess arises from the hindered rotation about the biaryl axis connecting to the two
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Kajiura, T.; Furumai, T.; Igarashi, Y.; Hori, H.; Higashi, K.; Ishiyama, T.; Uramoto, M.; Uehara, Y.; Oki, T. J. Antibiot. 1998, 51, 394-401
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Romaine, I. M.; Hempel, J. E.; Shanmugam, G.; Hori, H.; Igarashi, Y.; Polavarpu, P. L.; Sulikowshi, G. A. Org. Lett. 2011, 13, 4538-4541
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Hori, H.; Kajiura, T.; Igarashi, Y.; Furumai, T; Higashi, K.; Ishiyama, T; Uramoto, M; Uehara, Y; Oki, T. J. Antibiot., 2002, 55, 46-52
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Hori, H.; Kajiura, T.; Igarashi, Y.; Hori, H.; Higashi, K; Ishiyama, T.; Uramoto, M; Uehara, Y.; Oki, T. J. Antibiot. 2002, 55, 53-60
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Tatsuta, K.; Fukuda, T.; Ishimori, T.; Yachi, R.; Yoshida, S.; Hashimoto, H.; Hosokawa, S. Tetrahedron Lett., 2012, 53, 422-425
65:)-15--5,6,7,9,12,19-hexahydroxy-16-methoxy-4-propyl ;-3-oxapentacyclononadeca-1(11),12,15,18-tetraene-10,14,17-trione
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CCC1((((21(C(=O)c3c(cc4c(c3O)c(c(c(c4OC)OC)C5=C(C(=O)c6c(c(c7c(c6O)89(((C(9(C7=O)O)(O8)CCC)O)O)O)O)C5=O)OC)O)C2)O)O)O)O)O
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homocoupling. Recent work by multiple groups have shown the total synthesis of hibarimicinone and its derivatives.
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353:. The CLF/KS subunit is cleaved off by a thioesterase and modified by numerous steps (four oxidations, two
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Hori, H.; Higashi, K.; Ishiyama, T.; Uramoto, M.; Uehara, Y.; Oki, T. Tetrahedron Lett. 1996 37, 2785-2788
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369:. Finally, the hydroquinone on the same side of the previously mentioned ether oxidizes to form the
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dependent reductions, two methylations and decarboxylation) to form the final monomeric unit
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B. B. Liau, B. C. Milgram and M. D. Shair, J. Am. Chem. Soc., 2012, 134, 16765-16772
365:. Oxidative cyclization occurs on one end of the molecule to form the ether ring
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361:. Two monomer units undergo oxidative coupling to form the atropisomeric axis
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Dewick, Paul M. (2002). Medicinal
Natural Products. John Wiley and Sons, LTD
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Smyth, J.; Butler, N.; Keller, P. Nat. Prod. Rep. 2015, 32, 1562-1583
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identified a new class of molecule containing a dimeric-tetracyclic
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Except where otherwise noted, data are given for materials in their
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occur to form four six-membered cyclization and aromization
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Tatsuta, K.; Hosokawa, S. Chem. Rec., 2014, 14, 28-40
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526:3-Hydroxypropenals within hydroxyquinones
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380:Predicted Biosynthesis of Habarimicinone
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301:calmodulin-dependent protein kinase III
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161:Key: SSVUTDACAKUVQH-RNRCTZQLSA-N
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531:Heterocyclic compounds with 4 rings
506:Heterocyclic compounds with 5 rings
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373:species, giving hibarimicinone.
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243:(at 25 °C , 100 kPa).
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313:protein tyrosine kinase
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37:Preferred IUPAC name
233: g·mol
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516:Dimers (chemistry)
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287:. Analysis of the
276:Microbispora rosea
247:Infobox references
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536:Methoxy compounds
255:Chemical compound
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91:Interactive image
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309:protein kinase C
305:protein kinase A
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198:Chemical formula
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297:protein kinases
269:, derived from
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327:Biosynthesis
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271:hibarimicins
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72:Identifiers
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345:. Multiple
338:malonyl-CoA
311:(PKC), and
303:(CAMKIII),
191:Properties
521:Triketones
500:Categories
385:References
321:biomimetic
299:, such as
293:polyketide
283:region of
226:Molar mass
102:ChemSpider
78:3D model (
279:from the
136:101157796
317:monomers
289:bacteria
267:molecule
111:28289394
511:Phenols
371:quinone
307:(PKA),
231:924.858
123:PubChem
281:Hibari
265:small
175:SMILES
31:Names
355:NADPH
285:Japan
150:InChI
80:JSmol
367:(5)
363:(4)
359:(3)
351:(2)
343:(1)
126:CID
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446:^
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61:,9
57:,8
53:,7
49:,6
45:,5
41:(2
216:O
210:H
204:C
82:)
63:S
59:S
55:S
51:R
47:S
43:R
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