A UNIFIED TOTAL SYNTHESIS OF THE IMMUNOMODULATORS (-)-RAPAMYCIN AND (-)-27-DEMETHOXYRAPAMYCIN - ASSEMBLY OF THE COMMON C(1-20) PERIMETER AND FINAL ELABORATION

Authors
SMITH AB CONDON SM MCCAULEY JA LEAZER JL LEAHY JW MALECZKA RE
Citation
Ab. Smith et al., A UNIFIED TOTAL SYNTHESIS OF THE IMMUNOMODULATORS (-)-RAPAMYCIN AND (-)-27-DEMETHOXYRAPAMYCIN - ASSEMBLY OF THE COMMON C(1-20) PERIMETER AND FINAL ELABORATION, Journal of the American Chemical Society, 119(5), 1997, pp. 962-973
Citations number
73
Categorie Soggetti
Chemistry
Journal title
Journal of the American Chemical Society → ACNP
ISSN journal
00027863
Volume
119
Issue
5
Year of publication
1997
Pages
962 - 973
Database
ISI
SICI code
0002-7863(1997)119:5<962:AUTSOT>2.0.ZU;2-9
Abstract
The potent, naturally occurring immunomodulators (-)-rapamycin (1) and (-)-27-demethoxyrapamycin (2) have been synthesized via a unified and highly convergent strategy. In the preceding paper we discussed the c onstruction of common building blocks A-C and their linkage to provide the C(21-42) segments of 1 and 2. Herein we describe model studies of triene generation and hydroxyl deprotection, the preparation and coup ling of building blocks D and E, a two-step protocol for macrocycle fo rmation via union of the ABC and DE subtargets, and completion of the total syntheses. The synthesis of 27-demethoxyrapamycin (2) confirmed the assigned structure.