The synthesis of nine 2-substituted taurines (5a-i), including the marine natural product D-cysteinolic acid (5f), are described. These involve the successive conversion of N-t-butoxycarbonyl( Boc) -protected amino acid esters (I) into the N-Boc-2-aminoethanols (2), their 0-mesylated derivatives (3), the deprotected 2-aminoethyl methanesulphonates (4), followed by the replacement of the mesyloxy group by a sulpho group to give the optically active taurines (5a-e,g-i).Hydrogenolysis of 2-benzyloxymethyltaurine (5e) gives o-cysteinolic acid (5f). The structure of another of the products, (5b), is also confirmed by an alternative synthesis from N-Boc-valine methyl ester (1 b) via two P-bromoethylamine derivatives, (6b) and (7b).An optically active taurine derivative, D-cysteinolic acid (5f), has been isolated from marine micro-organisms and its bioactivity has also been r e p~r t e d .~ However, although the enantiomer of (50 has been prepared,' the natural product itself (5f) has not been synthesized before. Further, since there have been no simple and general synthetic routes to 2-substituted taurine derivatives (5), this has limited studies on the structural properties and structure-activity relationships for compounds of type (5).We earlier reported a general synthetic method leading to taurine-containing dipeptides, via an amino acid P-halogenoethylamide without r a~e m i z a t i o n ,~'~ and, more recently, we have shown that C-terminal amino acids in oligopeptides can be converted into taurine derivative^.^^^ We now report the extension of such a process to the synthesis of 2-substituted taurines: thus, a synthetic route represented by formulae (1)-(5) in the Scheme, has been evaluated as a general method: it proved remarkably successful.Syntheses.-2-Substituted taurines (5) were synthesized by two routes, namely through the 2-aminoethyl methanesulphonates (4) and the halogenoethylamine (7). The former shorter method proved better, although in the analogous conversion of a C-terminal amino acid of a peptide into a taurine derivative, the second route proved better.6.7 First, each a-amino acid methyl ester was converted into the corresponding hydroxyethylamide (2) by LiBH4 reduction8" in 80-95% yield. Then each hydroxyethylamide (2) was mesylated in 93-99% yield to give the derivative (3), which was deprotected to give (4) (ca. 90-100%), and subsequently allowed to react with sodium sulphite to give a 2-substituted taurine (5) (ca. 90-100%). Alternatively, the product (5b) was prepared from the substrate (3b) via two bromo intermediates (6b) and (7b) in 54% yield. The products derived from both syntheses proved identical.The natural D-cysteinolic acid (5f) was obtained quantitatively by a conventional hydrogenation of its benzyl derivative (5e), which was synthesized from Boc-L-Ser(Bz1)-OMe (le).
