Prunus Armeniaca Hydroxynitrile Lyase (ParHNL) Catalyzed Asymmetric Synthesis of δ,ε-Unsaturated Cyanohydrins

Abstract

A s y m m e t r i c S y n t h e s i s o f d , e -U n s a t u r a t e d C y a n o h y d r i n s Abstract: Hydroxynitrile lyases (HNL) are one of the key enzymes in cyanogenic plants, catalyzing the final step in the biodegradation pathway of cyanogenic glycosides releasing HCN and the corresponding carbonyl components. We have been able to find some new plant HNL from drupe available in the northern part of the Indian subcontinent. Asymmetric cyanohydrin synthesis from g,dunsaturated aldehydes by applying those new HNL is reported in this communication.Enantiomerically pure cyanohydrins have attracted the attention of organic chemists, as well as enzymologists, due to their immense potential as chiral building blocks and interesting biological properties. 1 Enantiopure cyanohydrins serve as intermediates for several industrially useful chemicals, and the use of chiral cyanohydrins as building blocks for the production of important chemicals is likely to continue growing, as it avoids problems associated with the optical resolution of or asymmetric synthesis of certain products. 2 One of the most promising and interesting ways to obtain enantiomerically pure cyanohydrins is the HNL-catalyzed addition of cyanide to the requisite carbonyl compound. 3 The chemistry and biology of HNL have been extensively explored over the past two decades, 4 and active research to find new HNL with interesting catalytic properties is still ongoing. Hydroxynitrile lyase has been reckoned as an efficient industrial biocatalyst for the production of active pharmaceutical ingredients (APIs), chiral building blocks, and agrochemicals. Both the alcohol and the nitrile parts of the cyanohydrin functionality can undergo transformation to a range of groups. These are general methods that proceed via racemization-free process so that the optical purity is retained. Pioneering work by Effenberger, Griengl, and others opened a new era in the area of asymmetric cyanohydrin synthesis by HNL, 4 readily available from the kernels of almond, apple, cherry, apricots, and plums.Hydroxynitrile lyase biocatalysis with a,b-unsaturated aliphatic aldehydes has been well reported in the literature. 5 However, HNL biocatalysis with structurally similar g,dunsaturated aldehydes has not been studied. The d,e-unsaturated cyanohydrins can serve as very good chiral intermediates for accessing various small organic molecules in asymmetric fashion as described by Marcus et al. 6 wUnsaturated chiral nitrones have been synthesized from d,e-unsaturated cyanohydrins and dipolar cycloaddition reactions afford highly substituted carbocyclic analogues in a stereoselective manner. The synthesized cyanohydrins from g,d-unsaturated aldehydes can also lead to various interesting small carbocyclic molecules by functional group modification.The required g,d-unsaturated aldehydes can be synthesized by a three-step method starting from allylic alcohols (Scheme 1). The allylic alcohols for accessing 1, 2, and 5 are commercially available; whereas the others were synthesized from th...