Synthesis of 7-deoxypancratistatin from carbohydrates by the use of olefin metathesis.
The stereocontrolled synthesis of (+)-7-deoxypancratistatin is described. The convergent synthesis has been achieved by two different strategies, both of which commence from a pentose and piperonal. The latter is converted into allylic bromide 7, which is then coupled with a protected methyl 5-deoxy-5-iodo-D-ribofuranoside in the presence of zinc metal. The first strategy involves a total of only 13 steps from D-ribose and piperonal, but suffers from a low yield in the zinc-mediated reaction between ribofuranoside 9, benzylamine, and bromide 7. The second strategy involves a total of 18 steps from D-xylose and piperonal. The former is converted into ribofuranoside 28, which is coupled with bromide 7 in the presence of zinc, and this is followed by ring-closing olefin metathesis. Subsequent Overman rearrangement, dihydroxylation, and deprotection then affords the natural product.
Center for Sustainable and Green Chemistry, Department of Chemistry, Building 201, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Anders E
AE
Håkansson
Anders
A
Palmelund
Henriette
H
Holm
Robert
R
Madsen
D000475:Alkenes / Q000737:chemistry*; D047151:Amaryllidaceae Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry*; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry
C418326:7-deoxypancratistatin; D000475:Alkenes; D047151:Amaryllidaceae Alkaloids; D000970:Antineoplastic Agents; D002241:Carbohydrates; D007546:Isoquinolines