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. 2008 Jun 19;10(12):2477-9.
doi: 10.1021/ol800749w. Epub 2008 May 20.

Total synthesis of the Hsp90 inhibitor geldanamycin

Hua-Li Qin  1 , James S Panek
Affiliations

Total synthesis of the Hsp90 inhibitor geldanamycin

Hua-Li Qin et al. Org Lett. .

Abstract

An enantioselective synthesis of the Hsp90 inhibitor geldanamycin was achieved in 20 linear steps and 2.0% overall yield from 2-methoxyhydroquinone. The synthesis is highlighted by a regio- and stereoselective hydroboration reaction; a Sc(OTf)(3)/Et(3)SiH-mediated pyran ring-opening reaction; an enantioselective crotylation to simultaneously install the C8-C9 (E) -trisubstituted olefin, the C10 and C11 stereocenters; a chelation-controlled asymmetric metallated acetylide addition; and an intramolecular copper(I)-mediated aryl amidation reaction to close the 19-membered macrolactam.

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Figures

Figure 1
Figure 1
Geldanamycin and related ansamycin antibiotics.
Scheme 1
Scheme 1
Retrosynthetic Analysis of Geldanamycin
Scheme 2
Scheme 2
Synthesis of Aromatic C6–C21 Fragment 7
Scheme 3
Scheme 3
Completion of the Total Synthesis of Geldanamycin
See this image and copyright information in PMC

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