Total Synthesis of the Epidermal Growth Factor Inhibitor (−)-Reveromycin B
- 3 March 2001
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 66 (7) , 2382-2393
- https://doi.org/10.1021/jo001646c
Abstract
The total synthesis of the epidermal growth factor inhibitor reveromycin B (2) in 25 linear steps from chiral methylene pyran 13 is described. The key steps involved an inverse electron demand hetero-Diels-Alder reaction between dienophile 13 and diene 12 to construct the 6,6-spiroketal 11 which upon oxidation with dimethyldioxirane and acid catalyzed rearrangement gave the 5,6-spiroketal aldehyde 9. Lithium acetylide addition followed by oxidation/reduction and protective group manipulation provided the reveromycin B spiroketal core 8 which was converted into the reveromycin A (1) derivative 6 in order to confirm the stereochemistry of the spiroketal segment. Introduction of the C1-C10 side chain began with sequential Wittig reactions to form the C8-C9 and C7-C6 bonds, and a tin mediated asymmetric aldol reaction installed the C4 and C5 stereocenters. The final key steps to the target molecule 2 involved a Stille coupling to introduce the C21-C22 bond, succinoylation, selective deprotection, oxidation, and Wittig condensation to form the final C2-C3 bond. Deprotection was effected by TBAF in DMF to afford reveromycin B (2) in 72% yield.Keywords
This publication has 32 references indexed in Scilit:
- Enantioselective Total Synthesis of Reveromycin BJournal of the American Chemical Society, 1998
- Synthetic Studies toward the Reveromycins: Asymmetric Synthesis of the Spiroketal Segment of Reveromycin BThe Journal of Organic Chemistry, 1997
- (±)-3,4,4a,5,6,7-HEXAHYDRO-4a,7,7-TRIMETHYL-1(2H)-NAPHTHALENONEOrganic Preparations and Procedures International, 1995
- Synthesis of chirally deuteriated phthalimido-propanols and evaluation of their absolute stereochemistryJournal of the American Chemical Society, 1988
- The Palladium‐Catalyzed Cross‐Coupling Reactions of Organotin Reagents with Organic Electrophiles [New Synthetic Methods (58)]Angewandte Chemie International Edition in English, 1986
- A facile chiral synthesis of (+)-Prelog–Djerassi lactonic acid methyl ester using five-membered heterocyclic chiral reagentsJournal of the Chemical Society, Chemical Communications, 1985
- Stereochemical control of reductions. 7. Reagent hinges: cis reduction of .beta.-octalones by internal delivery of chromium(II)The Journal of Organic Chemistry, 1983
- Macrolide total synthesis. The synthesis of seco-acid derivatives for the synthesis of methymycin and 10-deoxymethymycinThe Journal of Organic Chemistry, 1983
- Pheromonsynthesen ‐ Modellreaktionen zur Synthese von Polyether‐AntibiotikaEuropean Journal of Inorganic Chemistry, 1981
- REVERSIBLE FORMATION OF AMIDES FROM FREE CARBOXYLIC ACID AND AMINE IN AQUEOUS SOLUTION. A CASE OF NEIGHBORING GROUP FACILITATION1Journal of the American Chemical Society, 1961