Total Synthesis of (+)-Calyculin A and (−)-Calyculin B:  Cyanotetraene Construction, Asymmetric Synthesis of the C(26−37) Oxazole, Fragment Assembly, and Final Elaboration

Amos B Smith; Gregory K Friestad; Joseph Barbosa; Emmanuel Bertounesque; James J.-W Duan; Kenneth G Hull; Makoto Iwashima; Yuping Qiu; P. Grant Spoors; Brian A Salvatore

doi:10.1021/ja992135e

Journal article

Total Synthesis of (+)-Calyculin A and (−)-Calyculin B: Cyanotetraene Construction, Asymmetric Synthesis of the C(26−37) Oxazole, Fragment Assembly, and Final Elaboration

Amos B Smith, Gregory K Friestad, Joseph Barbosa, Emmanuel Bertounesque, James J.-W Duan, Kenneth G Hull, Makoto Iwashima, Yuping Qiu, P. Grant Spoors and Brian A Salvatore

Journal of the American Chemical Society, Vol.121(45), pp.10478-10486

11/17/1999

DOI: 10.1021/ja992135e

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Abstract

A convergent total synthesis leading to (+)-calyculin A and (−)-calyculin B (1 and 2), antipodes of the potent, highly selective and remarkably cell-permeable phosphatase inhibitors calyculins A and B, has been achieved. In the preceding paper we outlined the asymmetric synthesis of the C(9−25) spiroketal dipropionate subunit (+)-BC; herein we describe construction of the C(1−8) cyanotetraene, an asymmetric synthesis of the C(26−37) oxazole, fragment assembly and final elaboration to (+)-1 and (−)-2. Highlights of the synthesis include: application of a one-pot three-component Suzuki reaction for the construction of phosphonate A, a bifunctional triene precursor of the light sensitive C(1−8) cyanotetraene subunit, an asymmetric synthesis of the C(26−32) oxazole (−)-D, exploiting the Silks−Odom 77Se NMR protocol to assess enantiomeric purity, construction of the C(33−37) subtarget (−)-E in a highly stereocontrolled fashion via an acyliminium ion, and a concise, highly efficient sequence for fragment assembly and elaboration to (+)-calyculin A and (−)-calyculin B. The synthesis of (−)-2 also confirms the structure of calyculin B, previously based only on spectral comparison with calyculin A.

Details

Title: Subtitle: Total Synthesis of (+)-Calyculin A and (−)-Calyculin B: Cyanotetraene Construction, Asymmetric Synthesis of the C(26−37) Oxazole, Fragment Assembly, and Final Elaboration
Creators: Amos B Smith
Gregory K Friestad
Joseph Barbosa
Emmanuel Bertounesque
James J.-W Duan
Kenneth G Hull
Makoto Iwashima
Yuping Qiu
P. Grant Spoors
Brian A Salvatore
Resource Type: Journal article
Publication Details: Journal of the American Chemical Society, Vol.121(45), pp.10478-10486
Publisher: American Chemical Society
DOI: 10.1021/ja992135e
ISSN: 0002-7863
eISSN: 1520-5126
Language: English
Date published: 11/17/1999
Academic Unit: Chemistry
Record Identifier: 9983985858302771

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