Syntheses and properties of optically active 2-substituted taurines

Abstract

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).

Crystal structure of (2R)-1-[(methylsulfonyl)oxy]propan-2-aminium chloride: a chiral molecular salt

“…For background to chiral 2-amino-2-(alkyl/aryl/aralkyl)ethyl methanesulfonate hydrochlorides, see: Braghiroli & Di Bella (1996); Higashiura et al (1989); Morgan et al (1991); Pollack et al (1989); Xu (2002 Symmetry codes: (i) Àx; y À 1 2 ; Àz þ 2; (ii) Àx þ 1; y À 1 2 ; Àz þ 1; (iii) x À 1; y; z; (iv) Àx þ 1; y À 1 2 ; Àz þ 2; (v) x þ 1; y; z; (vi) Àx þ 1; y þ 1 2 ; Àz þ 2.…”

“…The chiral 2-amino-2-(alkyl/aryl/aralkyl)ethyl methanesulfonate hydrochlorides are useful starting materials for the preparation of amines, benzoates, thiobenzoates, sulfonic acids, etc., as methanesulfonate is a very good leaving group in nucleophilic substitution reactions. The chiral 2-(alkyl/aryl/aralkyl)ethanesulfonic acid derivatives and sulfonopeptides (Higashiura et al, 1989) occur in high concentrations in many mammalian tissues. These compounds are involved in various important physiological processes and are used as enzyme inhibitors and heptans in the development of catalytic anti-bodies (Braghiroli & Di Bella, 1996).…”

“…The title chiral molecular salt was synthesised as per the literature procedure (Higashiura et al, 1989). An aqueous solution of HCl (4 M, 12 ml) was added to a stirred solution of (2R)-2-[(tert-butoxycarbonyl)amino] propyl methanesulfonate (2.53 g, 10 mmol ) in dioxane (15 ml).…”

Facile synthesis of 1,1-[2H2]-2-methylaminoethane-1-sulfonic acid as a substrate for taurine α ketoglutarate dioxygenase (TauD)

“…16 This product (2) is converted to a mixed carbonic-carboxylic anhydride and reduced by the action of sodium borodeuteride, 17 which is commonly available at isotopic purity of >99.9%. 18 The deuterio alcohol (3) is converted to the mesylate (4), 19 and the mesylate is displaced by thioacetate. 20 The thioacetate ester (5) is oxidized by performic acid 21 and converted to the hydrochloride salt, which is triturated in absolute ethanol to yield the final product (6a), 1,1-[ 2 H 2 ]-methylaminoethane-1-sulfonic acid hydrochloride, with no detectable 1 H contamination as determined by 1 H NMR or mass spectral analysis, in 23% overall yield.…”

The first synthesis of optically active 1-substituted taurines

“…1-Substituted 2-aminoethanesulfonic acids (1-substituted taurines) and 2-substituted 2-aminoethanesulfonic acids (2-substituted taurines) are two types of structural analogues of naturally occurring amino acids for β-aminoalkanesulfonic acids. Optically active 2-substituted taurines have been synthesized effectively from optically active β-amino primary alcohols [3,[7][8][9][10][11][12][13][14][15][16], which were easily obtained by reduction of natural amino acids, via sulfite displacement of their methanesulfonates [7][8][9][10], or peroxy acid oxidation of their thioacetates [11][12][13][14][15], and sulfite ring opening of optically active aziridines [16]. But little attention has been paid to synthesis of 1-substituted taurines [13,[17][18][19].…”