Mycalamide A-药物合成数据库

【药物名称】Mycalamide A

化学结构式(Chemical Structure):

参考文献No.	579273
标题:	Total synthesis of mycalamide A and 7-epi-mycalamide A
作者:	Roush, W.R.; Pfeifer, L.A.
来源:	Org Lett 2000,2(6),859

合成路线图解说明: The Curtius degradation of carboxylic acid (XIV) with Ph2PON3 and 2-(trimethylsilyl)ethanol (A) gives the carbamate (XV), which is acylated with 2-(benzyloxy)acetyl chloride (XVI) and LiHMDS in THF, yielding the imide (XVII). The condensation of (XVII) with aldehyde (XVIII) by means of TiCl4 and DIEA in dichloromethane affords the expected adduct (XIX), which is oxidized with TFAA and DMSO in dichloromethane/DIEA, providing the beta-ketoimide (XX) as a diastereomeric mixture at the benzyloxy group. The cyclization of (XX) by means of CSA in methanol, followed by separation of the diastereomeric mixture, furnished the hydroxy tetrahydropyran derivative (XXI), which is submitted to a Swern oxidation to give the trahydropyranone (XXII). The reaction of (XXII) with diiodomethane, TiCl4 and Zn yields the exo-methylene compound (XXIII), which is desilylated with TBAF in DMF to afford intermediate (XXIV). Finally, this compound is submitted to a reductive cleavage of the benzyloxy and cyclic carbonate groups with Na/NH3 in THF/ethyl ether to furnish the target compound.

参考文献No.	605077
标题:	Diastereoselective synthesis of N-benzoyl mycalamine, the fully elaborated trioxadecalin nucleus of mycalamide A. Control of the key N-acyl aminal stereocenter via carbamate acylation
作者:	Roush, W.R.; Marron, T.G.
来源:	Tetrahedron Lett 1995,36(10),1581

合成路线图解说明: The methylation of the homoallyl alcohol (I) with methyl iodide and NaH in DMF gives the methyl ether (II), which is oxidized with O3, yielding the aldehyde (III). The diastereoselective allylation of (III) with the chiral borane (IV) in ethyl ether affords the homoallyl alcohol (V), which is epoxidized to the epoxide (VI). The cleavage of the epoxide (VI) with trichloromethyl carbonate provides the cyclic carbonate (VII), which is protected with Troc-Cl and pyridine and then oxidized with NaIO4, furnishing the aldehyde (VIII). The asymetric allylation of (VIII) with the chiral boronate (IX) gives the new homoallyl alcohol (X), which is treated with dimethyldioxirane (XI) to yield the epoxide (XII). Elimination of the Troc- group of (XII) with Zn/HOAc, followed by selective silylation with Tbdps-Cl and imidazole, affords the cyclized tetrahydropyran derivative (XIII), which is cyclized with P2O5 and formaldehyde, and oxidized with CrO3 and sulfuric acid to provide the bicyclic carboxylic acid (XIV).