Natural product synthesis frontalin

Enantiomerically pure tetrahydro-l//-pyrrolo[2, l -acrylamides derived from proline (see Section 11.11.7.4), are versatile intermediates for the synthesis of natural products or drugs. Compound 86a was submitted to debromination with Bu3SnH followed by ring opening in KOH and further reduction with BHj to give diol 89 that was then easily transformed into (A)-4-(2,2,4-trimethyl-l,3-dioxolan-4-yl)-lT>utanol 90, a key intermediate for )-frontalin, <2002TA155>,... 

The availability of 38C2 as a broad scope, enantioselective, efficient aldolase enzyme has had a significant impact on organic synthesis. Some of the molecules we have synthesized with 38C2 include the natural products ( + ) —frontalin [( + )— 27] (List et al., 1999), some brevicomins [( —) —28 and (—) —29] (List etal., 1998a), epothilones A (30) and C (31) (Sinha et al., 1998), and the Wieland-Miescher ketone [( ) — ( + )—32] (Hoffmann et al., 1998 Zhong et al., 1997). The brevicomin examples represent the first use of a catalytic antibody to decrease the total number of synthetic steps and increase the enantioselectivity of natural product syntheses. 

This was applied to the synthesis of beetle aggregation pheromones exo- and ewiio-brevicomin, exo-isobrevicomin and (-)-frontalin (Fig. 1.8). A volatile contributor of beer aroma was also synthesised [25, 26]. The synthesis of these natural products also showed the ability of ZrCU to successfully deprotect 1,3-dioxolane groups. 

A few carbon-substituted reagents (18)-(20) have also been prepared. Of these, reagent (18) has been used in the synthesis of frontalin, a natural product. The last three examples (21)-(23) show interesting steric and electronic effects on the regio- and stereoselectivity of the alkylation and condensation reactions. ... 

Other syntheses of natural products have capitalized on the 38C2-catalyzed aldol addition of hydroxyacetone to install 1,2-syn-diol functionality. Aldolase antibody 38C2 was also used for synthesis of brevicomins 59-61 (Scheme 6.7) [23] and 1-deoxy-L-xylulose (62) (Scheme 6.8) [24]. Antibody 38C2-catalyzed kinetic resolution of a tertiary aldol was used for the synthesis of (+)-frontalin (63) (Scheme 6.9) [10]. 

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