CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

For the synthesis of a nucleoside analog, a convergent approach, 159a-b,163 involving
the base coupling of a sugar unit with a nucleoside base using various established
procedures, 164 has an inherent advantage since it provides an opportunity to carry out a
desired chemical/stereochemical modification in the sugar unit prior to the coupling. Thus,
designing and developing efficient synthesis of sugar units assumes considerable
importance.
IV.3.2: Present work
The present work describes our endeavors to develop a very simple, efficient and
stereochemically flexible strategy for the synthesis of 3-C'-branched sugars of the
corresponding nucleosides (Scheme IV.3.1) through exploitation of the bimetallic redox
strategy for crotylation, discussed in chapter III. To this end, the required homoallylic
alcohol 83 was prepared by the coupling of the allylic bromide 82 with the aldehyde 1
(Chapter III.1.2) using the bi-metallic strategy. As evident from the diastereoselectivity of
the reaction (discussed in the previous chapter), the strategy provided efficient routes to
prepare all the four possible diastereomers 83a-d in substantial amounts. While 83c and
83d could be obtained as two major diastereomers directly from the coupling reaction, the
other two isomers 83a and 83b were prepared via an oxidation-reduction protocol. All
these are suitable templates for synthesizing nucleoside analogs of diverse stereochemical
feature. However, we had chosen 83d to perform a representative synthesis of 3'-Cbranched
2',3'-dideoxynucleoside analog.
163