title: Efficient synthesis of [3H]-sanglifehrin A via selective oxidation/reduction of alcohols at C31 and C35.
abstract: [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.
authors.affiliation: Novartis Institutes for BioMedical Research Basel, Transplantation Research, Novartis Pharma AG, Basel, Switzerland. juergen.wagner@novartis.com
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wagner
authors.forename: Hendrik
authors.initials: H
authors.lastname: Andres
authors.forename: Stefan
authors.initials: S
authors.lastname: Rohrbach
authors.forename: Dieter
authors.initials: D
authors.lastname: Wagner
authors.forename: Lukas
authors.initials: L
authors.lastname: Oberer
authors.forename: Julien
authors.initials: J
authors.lastname: France
mesh_terms: 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*
chemical_list: D000438:Alcohols; D007783:Lactones; D011868:Radioisotopes; D019163:Reducing Agents; D013141:Spiro Compounds; C121329:sanglifehrin A; D014316:Tritium