Total synthesis of (±)-Wortmannin

Angewandte Chemie - International Edition

Volumn 41, Issue 24, 2002, Pages 4680-4682

  Mizutani, Takashi ^a   Honzawa, Shinobu ^a   Tosaki, Shin Ya ^a   Shibasaki, Masakatsu ^a  

^a UNIVERSITY OF TOKYO   (Japan)

Author keywords

Heck reaction; Natural products; Phosphoinositide 3 kinase; Rearrangement; Total synthesis

Indexed keywords

ANDROSTANE DERIVATIVE; ENZYME INHIBITOR; WORTMANNIN; CARBON; DIOSPHENOL; PHENOL DERIVATIVE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; SYNTHESIS; CHEMICAL PARAMETERS; CHEMICAL REACTION; CLAISEN REARRANGEMENT;

ANDROSTADIENES; ENZYME INHIBITORS; MOLECULAR STRUCTURE;

CARBON; CHEMICAL REACTIONS; MOLECULAR STRUCTURE;

INHIBITORS;

SYNTHESIS (CHEMICAL);

EID: 0037121440     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200290014     Document Type: Article

References (29)

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13. This synthetic route would lead to an asymmetric total synthesis of 1 by using an asymmetric Heck reaction. For a review, see a) Y. Donde, L. E. Overman in Catalytic Asymmetric Synthesis, 2nd Ed. (Ed.: I. Ojima), Wiley-VCH, New York, 2000, pp. 675-697; b) M. Shibasaki, E. M. Vogl in Comprehensive Asymmetric Catalysis, Vol. 1 (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, New York, 1999, pp. 457-487; we actually succeeded in an efficient kinetic resolution with an asymmetric Heck reaction as shown in Scheme 4. Further conversions toward 1, however, have not been achieved so far, because of the problem of deprotection. Optimization using 4 is currently under investigation, see c) S. Honzawa, T. Mizutani, M. Shibasaki, Tetrahedron Lett. 1999, 40, 311-314.
14. This synthetic route would lead to an asymmetric total synthesis of 1 by using an asymmetric Heck reaction. For a review, see a) Y. Donde, L. E. Overman in Catalytic Asymmetric Synthesis, 2nd Ed. (Ed.: I. Ojima), Wiley-VCH, New York, 2000, pp. 675-697; b) M. Shibasaki, E. M. Vogl in Comprehensive Asymmetric Catalysis, Vol. 1 (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, New York, 1999, pp. 457-487; we actually succeeded in an efficient kinetic resolution with an asymmetric Heck reaction as shown in Scheme 4. Further conversions toward 1, however, have not been achieved so far, because of the problem of deprotection. Optimization using 4 is currently under investigation, see c) S. Honzawa, T. Mizutani, M. Shibasaki, Tetrahedron Lett. 1999, 40, 311-314.
15. This synthetic route would lead to an asymmetric total synthesis of 1 by using an asymmetric Heck reaction. For a review, see a) Y. Donde, L. E. Overman in Catalytic Asymmetric Synthesis, 2nd Ed. (Ed.: I. Ojima), Wiley-VCH, New York, 2000, pp. 675-697; b) M. Shibasaki, E. M. Vogl in Comprehensive Asymmetric Catalysis, Vol. 1 (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, New York, 1999, pp. 457-487; we actually succeeded in an efficient kinetic resolution with an asymmetric Heck reaction as shown in Scheme 4. Further conversions toward 1, however, have not been achieved so far, because of the problem of deprotection. Optimization using 4 is currently under investigation, see c) S. Honzawa, T. Mizutani, M. Shibasaki, Tetrahedron Lett. 1999, 40, 311-314.
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21. At this stage, the undesired diastereomer of 11 was recrystallized from acetone and an X-ray crystallographic analysis succeeded in confirming the stereochemistry. CCDC-191844 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www. ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ, UK; fax: (+ 44) 1223-336-033; or deposit@ccdc.cam.ac.uk).
22. The undesired diastereomer could be readily recycled to the desired diastereomer in several ways.
23. Intermolecular Michael addition of various reagents to the corresponding enone failed.
24. We tried other several strategies for the construction of wortmannin skeleton from 3 (Scheme 5). These strategies, however, were unsuccessful.
25. The stereochemistry of Ha was clearly determined by NOE measurements on 19, and that of Hb was also determined by the same method.
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29. When a minor diastereomer was used as a substrate for successive oxidations, only a low yield of 20 was obtained (ca. 10%).