Synthesis of (-)-LL-C10037α and Related Manumycin-Type Epoxyquinols

Peter Wipf; Yuntae Kim; Heike Jahn

doi:10.1055/s-1995-4141

Synthesis 1995; 1995(12): 1549-1561
DOI: 10.1055/s-1995-4141

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Synthesis of (-)-LL-C10037α and Related Manumycin-Type Epoxyquinols

Peter Wipf^* , Yuntae Kim, Heike Jahn

^*Department of Chemistry, University of Pittsburgh, Pennsylvania 15260, USA, Fax +1(412)6240787; E-mail pwipf+@pitt.edu

Abstract

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Starting with N-allyloxycarbonyl-protected 2,5-dimethoxyaniline, hypervalent iodine oxidation protocols and selective enone epoxidation provides the Streptomyces metabolite LL-C10037α in nine steps and 7-10% overall yield. In an asymmetric variant of this strategy, (R,R)-pentane-2,4-diol is used as a chiral acetalization agent. The resulting semiquinone spiroacetal, due to an ortho-acylamino substituent that restricts the 1,3-dioxane ring conformation, undergoes face-selective epoxidation and is further functionalized to give (-)-LL-C10037α in 94% ee. These pathways represent the first syntheses of the highly functionalized mC₇N core of the manumycins and have been further extended toward the preparation of analogs for SAR studies of this class of antitumor antibiotics. Manumycins inhibit the farnesylation of Ras-protein by PFTase (protein farnesyltransferase).

hypervalent iodine oxidation - face-selective enone epoxidation - chiral quinone monoketals - antitumor antibiotics

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