Fehrentz J A, Genu-Dellac C, Amblard M, Winternitz F, Loffet A, Martinez J
Laboratoire de Chimie et Pharmacologie de Molécules d'Intérêt Biologique, URA CNRS 1845, Faculté de Pharmacie, Montpellier, France.
J Pept Sci. 1995 Mar-Apr;1(2):124-31. doi: 10.1002/psc.310010204.
N-Urethane-protected N-carboxyanhydrides (UNCAs) are very reactive amino acid derivatives. They have been successfully used in peptide synthesis, in both solution and solid phase. We have demonstrated that UNCAs are interesting starting materials for the synthesis of various amino acid derivatives. Chemoselective reduction of UNCAs with sodium borohydride led the corresponding N-protected beta amino alcohols. Reaction of UNCAs with Meldrum's acid, followed by cyclisation, yielded enantiomerically pure tetramic acid derivatives. Diastereoselective reduction of tetramic acid derivatives produced [4S,5S)-N-alkoxycarbonyl-4-hydroxy-5-alkylpyrrolidin-2-ones derived from amino acids, which after hydrolysis yielded statine and statine analogues. Tetramic acid derivatives could also be obtained by reaction of UNCAs with benzyl ethyl malonate in the presence of sodium hydride to yield gamma-N-benzyloxycarbonylamino-beta-oxodicarboxyl esters followed by hydrogenolytic deprotection and decarboxylation. UNCAs also reacted with phosphoranes to produce the ketophosphorane in excellent yields. Subsequent oxidation with oxone or with [bis(acetoxy)-iodo]-benzene produced vicinal tricarbonyl derivatives. These reactions usually proceeded smoothly and with high yields.
N-氨基甲酸乙酯保护的N-羧基环内酸酐（UNCAs）是非常活泼的氨基酸衍生物。它们已成功用于溶液和固相的肽合成。我们已证明UNCAs是合成各种氨基酸衍生物的有趣起始原料。用硼氢化钠对UNCAs进行化学选择性还原得到相应的N-保护的β-氨基醇。UNCAs与丙二酸亚异丙酯反应，然后环化，得到对映体纯的四羰酸衍生物。四羰酸衍生物的非对映选择性还原产生了源自氨基酸的[4S,5S)-N-烷氧羰基-4-羟基-5-烷基吡咯烷-2-酮，水解后得到他汀和他汀类似物。四羰酸衍生物也可以通过在氢化钠存在下使UNCAs与苄基丙二酸乙酯反应，得到γ-N-苄氧基羰基氨基-β-氧代二羧酸酯，然后进行氢解脱保护和脱羧反应来获得。UNCAs还与磷叶立德反应，以优异的产率生成酮磷叶立德。随后用过一硫酸钾或[双(乙酰氧基)-碘代]苯氧化生成邻位三羰基衍生物。这些反应通常进行得很顺利，产率很高。
