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

Abstract

A variety of racemic epoxides mainly derived from terminal olefins,such as aliphatic epoxides, multifunctionalized epoxides and amine-substitutedepoxides, have been successfully resolved into the enantiomericallypure epoxides and diols using -Jacobsen’s hydrolytickinetic resolution (HKR) method. The chiral epoxides thus preparedwere further elaborated by synthetic manipulation to provide a varietyof compounds of biological interest. A general synthetic strategyfor the construction of SYN/ ANTI-1,3-polyol systems using iterativeHKR has been developed, which was subsequently utilized in the synthesisof natural products with a broad range of biological activity. Theprotocol for the 1,3-polyols was also further extended to the synthesisof 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)-Vigabatrinand ( S)-Dihydrokavain 3 Multifunctionalized Epoxides 3.1 Synthesis of (+)-Boronolide 4 Amine-Substituted Epoxides 4.1 Synthesis of Protected (2 R,4 S)-4-Hydroxyornithine 5 Development of a General Synthetic Strategy for the Constructionof 1,3-Polyols 6 Synthesis of Compounds Containing 1,3-Polyols and AminoAlcohols 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 Synthesisof (+)-Negamycin 7 Conclusion