Efficient synthesis of [3H]-sanglifehrin A via selective oxidation/reduction of alcohols at C31 and C35.
[Reaction: see text]. Sanglifehrin A is a novel complex natural product showing strong immunosuppressive activity and remarkably high affinity for cyclophilin A. To assess its pharmacokinetic properties in vivo, an efficient synthetic route was developed to introduce a tritium label in position C35 of sangliferin A via an oxidation/reduction strategy. The synthetic approach is particularly attractive, because the C35-oxo intermediate 7 is available in good yield on large scale and the reducing agent, lithium tri-sec-butylborotritide, is readily available. An attempt to apply a similar strategy to the alcohol in position C31 led primarily to C31-epi-hydroxy sanglifehrin A under a variety of conditions.
Wagner
Jürgen
J
Novartis Institutes for BioMedical Research Basel, Transplantation Research, Novartis Pharma AG, Basel, Switzerland. juergen.wagner@novartis.com
Andres
Hendrik
H
Rohrbach
Stefan
S
Wagner
Dieter
D
Oberer
Lukas
L
France
Julien
J
D000438:Alcohols / Q000737:chemistry*; D006868:Hydrolysis; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011868:Radioisotopes; D019163:Reducing Agents; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry; D014316:Tritium / Q000737:chemistry*
D000438:Alcohols; D007783:Lactones; D011868:Radioisotopes; D019163:Reducing Agents; D013141:Spiro Compounds; C121329:sanglifehrin A; D014316:Tritium