Study On Total Synthesis Of Dragonamide And Leucamide A

Dragonamide, an oceanic nature material, was total synthesized in the paper.And fragments of Leucamide A, an oceanic nature material too, were synthesized.Synthesis route to Dragonamide was designed. The molecule was made up withTetrapeptide A.15 and (R)-2-methyl-7-alkyl-octyl acid, A.28. They were coupledusing BOPCl as coupling reagent to give A.30. After cleavage of the t-butyl ester ofA.30, Dragonamide was achieved by activation with PyBOP and treatment withammonia in a yield of 10.9%.Tetrapeptide A.15 was prepared from L-Phe and L-Val in a yield of 32.5%, withO-nitrobenzenesulfonyl group and t-Butyl group as protecting groups.(R)-2-methyl-7-alkyl-octyl acid, A.28 was prepared from 1,5-pentanediol. Aftermonoprotection and Swern oxidation, aldehyde was got. Then it reacted with wittigreagent. After selective hydrogenation and hydrolyzation, the intermediate wascoupled with chiral auxiliary. Then alkylation of stereoselective was completed withNAHMDSA and MeI at -78 ℃ . Chiral auxiliary was removed, followed byesterification with diazomethane, hydrogenation and Swern oxidation to give anotheraldehyde. It was converted alkyne using the Ohira-Bestmann reagent.(R)-2-methyl-7-alkyl-octyl acid, A.28 was got after saponification in a yield of 17.1%and e.e. beyond 99%.Due to its NMR data and optical rotation data could not match them in reference,it was found that structure of dragonamide was wrong. Then(S)-2-methyl-7-alkyl-octyl acid was prepared using exactly the same procedure. Andcorrect Dragonamide was synthesized at finally in a total yield of 1.86%, andstructure was SSSSS not RSSSS.Synthesis route to Leucamide A was designed. The molecule was made up withB.12, B.20 and B.24 which were prepared in the paper.B.12 was given from coupling after removing protecting groups of B.10 and B.6.Dipeptide B.10 was obtained from L-Leu and L-Pro in a yield of 56.7%. In a similarway Dipeptide B.4 was got from L-Ser and L-Ala. After cyclodehydration withBurgess reagent and dehydrogenation with BrCCl3&DBU, the oxazole B.6 wasprepared in a yield of 46.8%.B.20 was obtained after removing protacting group of B.19. Dipeptide B.17 wasobtained from L-Ser and L-Thr through similar way, followed by oxidation withDess-Martin Periodinane and cyclodehydration with PPh3&I2 to givemethyloxazole B.19 in a yield of 36.5%.Activted intermediate B.24 was prepared from L-Val through coupling witho-diaminobenzene ,sulfuration and cyclodehydration.