Convergent syntheses of N-Boc-protected (2S,4R)-4-(Z)-propenylproline and 5-chloro-1-(methoxymethoxy)pyrrol-2-carboxylic acid - Two essential building blocks for the signal metabolite hormaomycin

Abstract

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-protected (2S,4R)-4-hydroxyproline, 7]. The O-MOM-protected 5-chloro-1-hydroxypyrrole-2-carboxylic acid [Chpca(MOM)-OH (29)] was prepared along a reasonably efficient synthetic route applying the thermal rearrangement of 2-azido-6-chloropyridine 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-hydroxypyrroles functionalized at C-2, was confirmed by the successful synthesis of Chpca-(3-Ncp)Ala-OFM 33 obtained from the acylated amino ester Chpca(MOM)-(3-Ncp)Ala-OFM 32, which was selectively deprotected leaving the sensitive N-hydroxypyrrole unit intact. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).