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Synlett 2009(9): 1367-1382  
DOI: 10.1055/s-0029-1217171
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© Georg Thieme Verlag Stuttgart ˙ New York

Hydrolytic Kinetic Resolution as an Emerging Tool in the Synthesis of Bioactive Molecules

Pradeep Kumar*, Priti Gupta
Division of Organic Chemistry, National Chemical Laboratory, Pune 411008, India
Fax: +91(20)25902629; e-Mail: pk.tripathi@ncl.res.in;
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Received 7 October 2008
Publikationsdatum:
13. Mai 2009 (online)

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Abstract

A variety of racemic epoxides mainly derived from terminal olefins, such as aliphatic epoxides, multifunctionalized epoxides and amine-substituted epoxides, have been successfully resolved into the enantiomerically pure epoxides and diols using ­Jacobsen’s hydrolytic kinetic resolution (HKR) method. The chiral epoxides thus prepared were further elaborated by synthetic manipulation to provide a variety of compounds of biological interest. A general synthetic strategy for the construction of syn/anti-1,3-polyol systems using iterative HKR has been developed, which was subsequently utilized in the synthesis of natural products with a broad range of biological activity. The protocol for the 1,3-polyols was also further extended to the synthesis of 1,3-amino alcohols.

1 Introduction

2 Aliphatic/Aromatic Epoxides

2.1 Synthesis of (R)- and (S)-Massoialactone

2.2 Synthesis of Iso-cladospolide B and Cladospolide B

2.3 Synthesis of Herbarumin III

2.4 Synthesis of Decarestrictine D

2.5 Concise Synthesis of (-)-Deoxoprosopinine

2.6 Synthesis of cis-Lauthisan

2.7 Synthesis of CMI-977 (LDP-977)

2.8 Synthesis of (S)-Betaxolol and (S)-Metoprolol

2.9 Synthesis of (S)-Vigabatrin and (S)-Dihydrokavain

3 Multifunctionalized Epoxides

3.1 Synthesis of (+)-Boronolide

4 Amine-Substituted Epoxides

4.1 Synthesis of Protected (2 R,4S )-4-Hydroxyornithine

5 Development of a General Synthetic Strategy for the Construction of 1,3-Polyols

6 Synthesis of Compounds Containing 1,3-Polyols and Amino Alcohols

6.1 Synthesis of Tarchonanthuslactone and Cryptocarya Diacetate

6.2 Synthesis of Strictifolione

6.3 Synthesis of the Lactone Moiety of Compactin

6.4 Synthesis of Verbalactone

6.5 Synthesis of Tetrahydrolipstatin

6.6 Synthesis of Decarestrictine J

6.7 Construction of a 1,3-Amino Alcohol: Application to the Synthesis of (+)-Negamycin

7 Conclusion

Key words

hydrolytic kinetic resolution - terminal epoxides - natural products - synthesis - biological activity

3

For information, see: http://www.Rhodiachirex.com.

51

Kumar, P.; Naidu, S. V. unpublished results

53

Kumar, P.; Naidu, S. V. unpublished results

56

Cherian, S. K.; Naidu, S. V.; Kumar, P. unpublished results.

58

Tripathi, D.; Kumar, P. unpublished work.

61

Choudhary, P. S.; Gupta, P.; Kumar, P. unpublished work.