Development of a Practical Multikilogram Production of (R)-Seudenol by Enzymatic Resolution

Abstract

Different enzymatic routes for the production of (R)-seudenol were investigated. The Novozym 435-catalyzed reaction of racemic seudenol with vinyl butyrate proved to be the most promising route. By using vinyl laurate as an acyl donor, (R)-seudenol laurate could be separated from (S)-seudenol by an extractive work-up procedure. A nonaqueous hydrolysis allowed the isolation of pure (R)-seudenol. Scaling up to 7 kg resulted in a robust reproducible process.

A Potent Mimetic of the Siglec‐8 Ligand 6’‐Sulfo‐Sialyl Lewisx

“…The enzymatic separation of the enantiomeric mixture raccis-31 using the lipase Novozyme 435 and vinyl butyrate yielded the butyrate 32 in 35 % yield. [48,49] To determine its absolute configuration, ester 32 was hydrolyzed to acid 33. Its optical rotation was in agreement with a literature value of the desired (1S,3R)-(+)-3-hydroxycyclohexane-1-carboxylate (33, [α] D 20 + 10.3 vs. + 10.7 [50] ), The synthesis of acceptor 35 was completed by reduction with DIBAL-H (!34), followed by the regioselective protection of the primary hydroxyl group with Table 1.…”

Total Synthesis of (+)-Aplykurodinone-1

“…The bicyclic core structure of RS-2 may be constructed via an intramolecular carbonyl–ene cyclization, while the quaternary stereochemical center in RS-3 may be constructed via an Ireland–Claisen rearrangement. Intermediate RS-4 may be generated from the coupling of ( R )-citronellic acid and ( R )-seudenol, which can be readily prepared from pulegone and 3-methylcyclohexenone, respectively …”

Synthetic Studies of Kinamycin Antibiotics: Stereoselective Synthesis of the Highly Oxygenated D‐Ring and Construction of the ABD‐Ring System of Kinamycins

“…This study also achieved the construction of α‐naphthylcyclohexenone 22 , a highly functionalized intermediate that could provide access to the tetracyclic ring system of the kinamycins. Furthermore, the chemistry that was developed here may be amenable to asymmetric synthesis given that access to optically active material can be achieved by either the enzymatic resolution30 of racemic allylic alcohol 2 or the chiral reduction31 of cyclohexenone 1 . Studies toward the conversion of 22 into benzofluorenone 24 and kinamycin F are currently in progress.…”