17 抗HIV活性を有する海洋産環状デプシペプチド・パプアミド類の全合成研究(口頭発表の部)
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Papuamides A (1) and B (2) are novel cyclic depsipeptides isolated from the sponges collected at Papua New Guinea by Boyd and co-workers in 1999. They are known to inhibit the infection of human T-lymphoblastoid cells by HIV-1_<RF> in vitro. In addition to their novel biological activities, they have intriguing structures containing (4Z,6E)-2,3-dihydroxy-2,6,8-trimethyldecanoic acid (Dhtda) and 7 unusual amino acid residues. The stereochemistry of papuamides remains to be determined because of the uncertainty regarding the 3-OMeTyr and Dhtda parts. Recently we have clarified the absolute stereochemistry of 3-OMeTyr as (2R,3R). In this symposium we disclose our efforts on the structural determination of Dhtda and synthetic studies of papuamide B Dhtda-Gly part was synthesized by using stereoselective addition of alkynyl lithium generated from dibromoalkene (4) in situ to aldehyde (5) as a key step. Other diastereomers were synthesized according to the same procedure. The synthesis of (2R,3R)-3-OHLeu (22) and (2R,3R)-3-OMeTyr (29) were achieved by the use of asymmetric hydrogenation via dynamic kinetic resolution catalyzed by the chiral ruthenium or iridium complex originally developed by us. Other unusual amino acid residues, (2S,3S,4R)-DiMeGln (37) and (2S,3R)-Dab (42), were synthesized by diastereoselective Michael addition to chiral bicyclic lactam (30) and proline catalyzed asymmetric hydrazination of aldehyde (38) as a key step, respectively. The macrolactamization of heptapeptide (48) was achieved by FDPP as a coupling reagent. The consecutive coupling of cyclodepsipeptide (49), DiMeGln (37), Dab (42), Thr, and (2R,3S,8R)-Dhtda-Gly unit (16) using DEPBT followed by deprotection afforded (2R,3S,8R)-Dhtda-papuamide B (2). The synthesis of other isomers derived from Dhtda with different stereochemistry has been actively underway.
- 2007-08-24
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関連論文
- 17 抗HIV活性を有する海洋産環状デプシペプチド・パプアミド類の全合成研究(口頭発表の部)
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