Convergent Syntheses of N-Boc-Protected(2S,4R)-4-(Z)-Propenylproline and 5-Chloro-l-(methoxymethoxy)pyrrol-2-carboxylic Acid-Two Essential Building Blocks for the Signal Metabolite Hormaomycin

摘要

An efficient and scalable synthesis of enantiomerically pure N-Boc-protected 4-(Z)-propenylproline(15)using the conventional Wittig reaction to construct the double bond has been developed[11% yield over 8 steps from N-Boc-pro-tected(2S,4R)-4-hydroxyproline,7],The O-MOM-protected 5-chloro-l-hydroxypyrrole-2-carboxylic acid[Chpca(MOM)-OH(29)]was prepared along a reasonably efficient synthetic route applying the thermal rearrangement of 2-azido-6-chlo-ropyridine N-oxide(22)as a key step in fairly good overall yield[9% over 7 steps from easily accessible 2,6-dichloro-pyridine N-oxide(21)[.The suitability of the MOM-protected N-hydroxy group during the preparation of the N-hydroxy-pyrroles functionalized at C-2,was confirmed by the successful synthesis of Chpca-beta-Ncp)Ala-OFM 33 obtained from the acylated amino ester Chpca(MOM)-beta-Ncp)Ala-OFM 32,which was selectively deprotected leaving the sensitive N-hydroxypyrrole unit intact.