Serine derivatives, Mitsunobu reaction

The strategy was chosen to (1) link the amino acid derivative to a polystyrene-supported hydroxylamine, (2) carry out the cyclization under Mitsunobu conditions, and (3) assemble a short peptide on the free amino group present in the ring. This approach has been shown to be suitable particularly for solid-phase synthesis, as the supported (3-lactam could be easily separated from the by-products of the Mitsunobu reaction. The linker employed was a polystyrene resin carrying 0-trityl-hydroxylamine linker, prepared according to the literature procedure [151]. After the deprotection of Fmoc group carried out with 20% piperidine in DMF, the L-cbz-serine (or L-cbz-threonine) was coupled using (4,6-Dimethoxy-[l, 3, 5]-triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM) [152] in M-methylpyrrolidone (NMP) in the presence of M,M-diisopropylethylamine (DIPEA) (Schemes 42 45). 

As the structure of the side chain of the pyrimidine moiety remained uncertain until the very final stage of the structure elucidation, we proceeded to synthesize the most probable candidate for the structure of this moiety to compare with the natural sample. Relevant methodology was required to acquire the skeleton of BLM and we found a new synthon diethoxyacetamidine (8) for the efficient preparation of multifunctional pyrimidine (9), which was readily converted into the key aldehyde (10) (Fig. 10) [37]. The p-aminoalanin-amide moiety (7) was synthesized by Mitsunobu reaction of serine derivative (6)... 

As already mentioned, applications of the Mitsunobu reaction in lactone formation are significantly less common. Like so many other applications of the Mitsunobu reaction, the application of the Mitsunobu reaction for the preparation of lactones was first reported by Mitsunobu s group.Later on, Mitsunobu s group used the reaction to prepare colletodiol. Since then the scope of the reaction has been expanded to include the well known application of the Mitsunobu reaction for the preparation of amine protected (5)-3-amino-2-oxetanones derived from the correspondingly protected serine precursor this protocol was initially discovered by Vederas and... 

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