Warning: Undefined array key "mm" in /www/wwwroot/www.ai-bt.com/si.php on line 10 Deprecated: trim(): Passing null to parameter #1 ($string) of type string is deprecated in /www/wwwroot/www.ai-bt.com/si.php on line 10 Toward a more step-economical and scalable synthesis of spongistatin 1 to facilitate cancer drug development efforts.

Literature DB >> 25165503

Toward a more step-economical and scalable synthesis of spongistatin 1 to facilitate cancer drug development efforts.

Abstract

An efficient, step-economical, and scalable synthesis of a diene-bearing AB spiroketal fragment of spongistatin 1, and a demonstration of its efficient coupling to an aldehyde derived from silylformylation of a homopropargyl alcohol to produce the entire complex C(13)-C(17) linker region are described. The scalability of the synthesis of the AB spiroketal fragment was demonstrated by the preparation of 34.5 grams by one chemist in ~60 workdays, and more than 40 grams overall. With this material in hand and having established a method for its efficient coupling to the CD fragment, we have set the stage for the rapid synthesis and evaluation of a series of analogs of the CD spiroketal.

Entities: Chemical Disease Gene Species

Year: 2013 PMID： 25165503 PMCID： PMC4142563 DOI： 10.1039/C3SC22186E

Source DB: PubMed Journal: Chem Sci ISSN： 2041-6520 Impact factor: 9.825

19 in total

1. The Spongistatins: Architecturally Complex Natural Products-Part One: A Formal Synthesis of (+)-Spongistatin 1 by Construction of an Advanced ABCD Fragment Financial support was provided by the National Institutes of Health (National Cancer Institute) through Grant CA-70329, NIH Postdoctoral Fellowships to A.M.B. and W.H.M., a Japan Society for Promotion of Science Fellowship to N.M., and a Royal Society Fulbright Fellowship to V.A.D. We also thank the Daiichi Pharmaceutical Co., Ltd, and the Tanabe Seiyaku Co., Ltd for financial support. Finally we thank Dr. George T. Furst, Dr. Patrick J. Carroll, Dr. Rakesh Kohli, and Mr John Dykins of the University of Pennsylvania Spectroscopic Service Center for assistance in securing and interpreting high-field NMR spectra, X-ray crystal structures, and mass spectra.

Authors: Amos B. Smith III; Victoria A. Doughty; Qiyan Lin; Linghang Zhuang; Mark D. McBriar; Armen M. Boldi; William H. Moser; Noriaki Murase; Kiyoshi Nakayama; Masao Sobukawa
Journal: Angew Chem Int Ed Engl Date: 2001-01-05 Impact factor: 15.336

2. Spongipyran Synthetic Studies. Evolution of a Scalable Total Synthesis of (+)-Spongistatin 1.

Authors: Amos B Smith; Chris Sfouggatakis; Christina A Risatti; Jeffrey B Sperry; Wenyu Zhu; Victoria A Doughty; Takashi Tomioka; Dimitar B Gotchev; Clay S Bennett; Satoshi Sakamoto; Onur Atasoylu; Shohei Shirakami; David Bauer; Makoto Takeuchi; Jyunichi Koyanagi; Yasuharu Sakamoto
Journal: Tetrahedron Date: 2009-09-15 Impact factor: 2.457

3. Design, synthesis, and biological evaluation of diminutive forms of (+)-spongistatin 1: lessons learned.

Authors: Amos B Smith; Christina A Risatti; Onur Atasoylu; Clay S Bennett; Junke Liu; Hongsheng Cheng; Karen TenDyke; Qunli Xu
Journal: J Am Chem Soc Date: 2011-08-12 Impact factor: 15.419

4. The stereocontrolled total synthesis of altohyrtin A/spongistatin 1: fragment couplings, completion of the synthesis, analogue generation and biological evaluation.

Authors: Ian Paterson; David Y-K Chen; Mark J Coster; José L Aceña; Jordi Bach; Debra J Wallace
Journal: Org Biomol Chem Date: 2005-05-24 Impact factor: 3.876

5. Spongipyran Synthetic Studies. Total Synthesis of (+)-Spongistatin 2.

Authors: Amos B Smith; Qiyan Lin; Victoria A Doughty; Linghang Zhuang; Mark D McBriar; Jeffrey K Kerns; Armen M Boldi; Noriaki Murase; William H Moser; Christopher S Brook; Clay S Bennett; Kiyoshi Nakayama; Masao Sobukawa; Robert E Lee Trout
Journal: Tetrahedron Date: 2009-08-15 Impact factor: 2.457

6. Multigram synthesis of the C29-C51 subunit and completion of the total synthesis of altohyrtin C (spongistatin 2).

Authors: Clayton H Heathcock; Mark McLaughlin; Jesus Medina; Jed L Hubbs; Grier A Wallace; Robert Scott; Michele M Claffey; Christopher J Hayes; Gregory R Ott
Journal: J Am Chem Soc Date: 2003-10-22 Impact factor: 15.419

7. Altohyrtins B and C and 5-desacetylaltohyrtin A, potent cytotoxic macrolide congeners of altohyrtin A, from the Okinawan marine sponge Hyrtios altum.

Authors: M Kobayashi; S Aoki; H Sakai; N Kihara; T Sasaki; I Kitagawa
Journal: Chem Pharm Bull (Tokyo) Date: 1993-05 Impact factor: 1.645

8. Complex fragment coupling by crotylation: A powerful tool for polyketide natural product synthesis.

Authors: Samuel K Reznik; Brian S Marcus; James L Leighton
Journal: Chem Sci Date: 2012-11-01 Impact factor: 9.825

9. Gram-scale synthesis of (+)-spongistatin 1: development of an improved, scalable synthesis of the F-ring subunit, fragment union, and final elaboration.

Authors: Amos B Smith; Takashi Tomioka; Christina A Risatti; Jeffrey B Sperry; Chris Sfouggatakis
Journal: Org Lett Date: 2008-08-28 Impact factor: 6.005

Toward a more step-economical and scalable synthesis of spongistatin 1 to facilitate cancer drug development efforts.

2. Spongipyran Synthetic Studies. Evolution of a Scalable Total Synthesis of (+)-Spongistatin 1.

3. Design, synthesis, and biological evaluation of diminutive forms of (+)-spongistatin 1: lessons learned.

4. The stereocontrolled total synthesis of altohyrtin A/spongistatin 1: fragment couplings, completion of the synthesis, analogue generation and biological evaluation.

5. Spongipyran Synthetic Studies. Total Synthesis of (+)-Spongistatin 2.

6. Multigram synthesis of the C29-C51 subunit and completion of the total synthesis of altohyrtin C (spongistatin 2).

7. Altohyrtins B and C and 5-desacetylaltohyrtin A, potent cytotoxic macrolide congeners of altohyrtin A, from the Okinawan marine sponge Hyrtios altum.

8. Complex fragment coupling by crotylation: A powerful tool for polyketide natural product synthesis.

9. Gram-scale synthesis of (+)-spongistatin 1: development of an improved, scalable synthesis of the F-ring subunit, fragment union, and final elaboration.

10. Direct and highly regioselective and enantioselective allylation of β-diketones.

Review 1. Natural Products in the "Marketplace": Interfacing Synthesis and Biology.

2. Exploiting pseudo C2-symmetry for an efficient synthesis of the F-ring of the spongistatins.

3. A highly step-economical synthesis of dictyostatin.

4. Beyond the Roche ester: a new approach to polypropionate stereotriad synthesis.

5. Design and 22-step synthesis of highly potent D-ring modified and linker-equipped analogs of spongistatin 1.

6. Hydroxyl-directed stereoselective diboration of alkenes.