First regioselective enzymatic alkoxycarbonylation of primary amines. Synthesis of novel 5'- and 3'-carbamates of pyrimidine 3',5'-diaminonucleoside derivatives including BVDU analogues

J Org Chem. 2004 Mar 5;69(5):1748-51. doi: 10.1021/jo035678m.

Abstract

The first regioselective enzymatic alkoxycarbonylation of primary amino groups has been achieved in pyrimidine 3',5'-diaminonucleoside derivatives. Thus, Candida antarctica lipase B (CAL-B) catalyzed this reaction with nonactivated homocarbonates allowing the selective synthesis of several N-5' carbamates, including (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) analogues, with moderate-high yields, whereas immobilized Pseudomonas cepacia lipase (PSL-C) afforded mixtures of alkoxycarbonylated regioisomers. To obtain N-3' carbamates selectively, a short and efficient chemoenzymatic route was used employing some of the N-5'-protected derivatives previously synthesized.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Bromodeoxyuridine / analogs & derivatives*
  • Bromodeoxyuridine / chemical synthesis*
  • Bromodeoxyuridine / chemistry
  • Carbamates / chemical synthesis*
  • Carbamates / chemistry
  • Enzymes, Immobilized / metabolism
  • Fungal Proteins
  • Lipase / metabolism
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Nucleosides / chemical synthesis*
  • Nucleosides / chemistry
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Stereoisomerism

Substances

  • Amines
  • Carbamates
  • Enzymes, Immobilized
  • Fungal Proteins
  • Nucleosides
  • Pyrimidines
  • Lipase
  • lipase B, Candida antarctica
  • Bromodeoxyuridine