93752-54-6

Upstream product

• 106-51-4 p-benzoquinone 
• 1560848-58-9 (1S,5S,6R)-3-azido-5-[(tert-butyldimethylsilyl)oxy]-7-oxabicyclo[4.1.0]hept-3-en-2-one 
• 1560848-54-5 (1R,3S,5R,6S,7S)-6-[(tert-butyldimethylsilyl)oxy]-8-[(1R)-1-(4-methoxyphenyl)ethyl]-4-oxa-8-azatricyclo[5.1.0.0^3,5]octan-2-one 
• 1560848-51-2 (1R,5R,6S)-5-[(tert-butyldimethylsilyl)oxy]-7-[(1R)-1-(4-methoxyphenyl)ethyl]-7-azabicyclo[4.1.0]hept-3-en-2-one 
• 1560848-42-1 (1R,5R,6S)-5-[(tert-butyldimethylsilyl)oxy]-7-[(1R)-1-(4-methoxyphenyl)ethyl]-7-azabicyclo[4.1.0]heptan-2-one 
• 627873-21-6 (1aR,3aR,6aS,6bS)-1-(4-Methoxy-benzyl)-5,5-dimethyl-hexahydro-4,6-dioxa-1-aza-cyclopropa[e]inden-2-one 
• 355401-57-9 (3aR,7aS)-6-iodo-2,2-dimethyl-3a,4,5,7a-tetrahydro-1,3-benzodioxol-5-one 
• 179949-73-6 4-(tert-Butyl-dimethyl-silanyloxy)-2-iodo-cyclohex-2-enone 
• 121651-99-8 (4S,5R)-4,5-O-isopropylidenedioxycyclohex-2-en-1-one 
• 1560848-59-0 N-[(1S,5S,6R)-5-[(tert-butyldimethylsilyl)oxy]-2-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl]acetamide 
• 174531-90-9 (2R,4R,7S,8R,9S)-11-<(allyloxycarbonyl)amino>-9-(tert-butyldiphenylsilyloxy)-7,8-epoxy-2,4-dimethyl-1,5-dioxaspiro<5.5>non-10-ene 
• 174591-71-0 (2S,3R,4S)-6--4-(tert-butyldiphenylsilyloxy)-2,3-epoxycyclohex-5-enone 
• 174591-70-9 (2S,3R,4S)-6-<(allyloxycarbonyl)amino>-4-(tert-butyldiphenylsilyloxy)-2,3-epoxycyclohex-5-enone 
• 174531-88-5 (2R,4R,7S,8R)-11-<(allyloxycarbonyl)amino>-7,8-epoxy-2,4-dimethyl-1,5-dioxaspiro<5.5>non-10-en-9-one 

Relevant academic research and scientific papers

Use of aziridines for the stereocontrolled synthesis of (-)-LL-C10037α, (+)-MT35214, and (+)-4-epi-MT35214

Strategies for the synthesis of the title compounds have been developed using a diastereoselective aziridination reaction of 4-O-substituted cyclohexenones. Aziridination using a chiral amine permitted resolution of a 4-hydroxycyclohexane derivative, and this resulted in the synthesis of both enantiomers of the title compound. Alternatively, the chiral 4-hydroxycyclohexenone starting material was derived from quinic acid. In both cases stereoselective epoxidation and opening of the aziridine ring with hydrazoic acid afforded the 2-azidocyclohexenone, which was transformed to the 2-acetamido group present in the natural product.

New Stereoselective Route to the Epoxyquinol Core of Manumycin-Type Natural Products. Synthesis of Enantiopure (+)-Bromoxone, (-)-LL-C10037α, and (+)-KT 8110

A practical route is decribed for the preparation of the C7N core of manumycin-type compounds. Starting from p-benzoquinone, optically pure compounds in both forms can be prepared via enzymatic resolution of a derived diacetoxy conduritol. A diepoxy aminoinositol is accessible which can function for formation of enantiopure epoxyquinones and quinols. Examples are given for acylation reactions of this amine with several acyl derivatives. With this approach (-)-LL-C10037α and quinones such as (+)-KT-8110 with 5A,6S-configuration can be synthesized through oxidation. In addition a short route to (+)-bromoxone is described. Most steps include simple epoxide formation and cleavage reactions which all can be carried out in a high stereoselective manner.

Enantioselective synthesis of (-)-LL-C10037α from benzoquinone

(formula presented) The enantioselective total synthesis of the Streptomyces metabolite (-)-LL-C10037α has been accomplished in 10 steps and 20% overall yield. An early chiral intermediate was resolved with Candida rugosa lipase to provide (+)-5 with an e

Synthesis of (-)-LL-C10037α and related manumycin-type epoxyquinols

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).

Biosynthesis of Antibiotic LL-C10037α: The Steps beyond 3-Hydroxyanthranilic Acid

The six steps from 3-hydroxyanthranilic acid to the epoxyquinol LL-C10037α, 1, produced by Streptomyces LL-C10037 have been determined by whole-cell feedings with deuterated substrates and by cell-free studies. 3-Hydroxyanthranilic acid, 2, is decarboxylated to 2-hydroxyaniline, 11, and then oxidized to 2,5-dihydroxyaniline, 8.Acetylation at nitrogen and oxidation afford acetamido-1,4-benzoquinone, 4.A crude cell-free preparation has been found to epoxidize 4 to the epoxyquinone 16 in the presence of O2 and either NaDH or NADPH.Reduction of 16 yields 1.Therelationship of this pathway to that of fungi that produce patulin via analogous intermediates from 6-methylsalicylic acid is discussed.