A new chemo-enzymatic approach to the stereoselective synthesis of the flavors tetrahydroactinidiolide and dihydroactinidiolide

The alcohols cis-5-hydroxy-cyclogeraniol and cis-alpha-epoxy-cyclogeraniol can be easily prepared with high diastereoisomeric purity starting from ethyl-alpha-cyclogeraniate. A few straightforward chemical transformations allow their conversion into tetrahydroactinidiolide and dihydroactinidiolide, two relevant natural flavors of carotenoid origin. The two starting C-10 alcohols can also be obtained in enantioenriched form by means of an optimized lipase-mediated resolution procedure. The fractional crystallization of the obtained enantioenriched tetrahydroactinidiolide proved to be very efficient, allowing the preparation of both tetrahydroactinidiolide and dihydroactinidiolide in enantiopure form (ee >98%). Finally, a comprehensive study on the oxidation of tetrahydroactinidiolide to dihydroactinidiolide was accomplished by devising a new selenium-free chemical process for this type of transformation. (C) 2015 Elsevier Ltd. All rights reserved.