A General Route to the Synthesis of N-Protected 1-Substituted and 1,2-Disubstituted Taurines

Abstract

S y n t h e s i s o f N -P r o t e c t e d 1 -S u b s t i t u t e d a n d 1 , 2 -D i s u b s t i t u t e d T a u r i n e sAbstract: N-Benzyloxycarbonyl protected a-substituted and a,bdisubstituted taurines were synthesized from olefins and epoxides via N-benzyloxycarbonylamino alcohol thioacetates as key intermediates. They are important sulfur analogues of naturally occurring amino acids and building blocks for the synthesis of asubstituted and a,b-disubstituted b-sulfonopeptides.There is a growing interest in the structural modification of natural peptides to overcome the limitations associated with their development as therapeutically useful agents, and to gain information on the nature and mechanism of the peptide-receptor interactions. 1-3 The phosphonamidate, phosphonate and sulfonamide-linked peptides are very important modified peptides and are recognized to be able to mimic transition-state analogues of hydrolysis of ester and amide bonds because of their tetrahedrally structural properties. During the last decade aminoalkylphosphonic acid and aminoalkanesulfonic acid derivatives, and phosphonopeptides and sulfonopeptides have been used as enzyme inhibitors and haptens in the development of catalytic antibodies. 4-7 Sulfonopeptides are more stable under both mildly acidic and basic conditions compared to phosphonopeptides and will be used more widely. b-Aminoalkanesulfonic acids are very important sulfur analogues of naturally occurring amino acids for the synthesis of sulfonopeptides because a-aminoalkanesulfonic acids and their derivatives are unstable. 8 There are three types of structural analogues of naturally occurring amino acids for b-aminoalkanesulfonic acids, which include 1-substituted taurines, 2-substituted taurines, and 1,2-disubstituted taurines (Figure 1). 2-Substituted taurines have been synthesized effectively from b-amino primary alcohols, 9-18 which were easily obtained by reduction of natural amino acids, from b-amino secondary alcohols 19,20 via sulfite displacement of their methanesulfonates, 9-12 peroxy acid oxidation of their thioacetates, 13-17,21 and sulfite ringopening of aziridines. 18 But little attention has been paid to the synthesis of 1-substituted and 1,2-disubstituted taurines 15,21,22 and their sulfonopeptides. 21,23,24 To synthesize structurally diverse sulfonopeptides, it is very important to develop an effective and general method for the preparation of 1-substituted and 1,2-disubstituted taurines. Herein we describe a general route to 1-substituted and 1,2-disubstituted taurines from olefins and epoxides. Figure 1 Taurine and substituted taurinesAs part of a program to synthesize structurally diverse sulfur analogues of naturally occurring amino acids, we sought to prepare 1-substituted and 1,2-disubstituted taurines. 1,2-Amino secondary alcohols are important key intermediates for synthesizing 1-substituted taurines. They could be prepared from available terminal olefins or 1,2-epoxyalkanes. Although alkenes could be converted to 1,2-N-protected amino alcohols di...

An efficient and facile synthesis of N-Cbz-β-aminoalkanesulfonamides

“…Our group modified the method to avoid the formation of the Michael adduct. In our procedure, DEAD and triphenylphosphine were mixed first to form a white precipitate of the active intermediate, the adduct of DEAD and triphenylphosphine, and subsequently a solution of an N-Cbz-amino alcohol and thiolacetic acid was added slowly into the reaction mixture [35,36]. Following our modified procedure, a series of thiolacetates 2ag were prepared in satisfactory to good yields from 42% to 82% (Table 1).…”

Negative‐ion electrospray ionization mass spectrometry of N‐benzyloxycarbonyl‐protected 1‐substituted and cyclic taurines

“…β ‐Aminoalkanesulfonic acids, including 1‐substituted β ‐aminoethanesulfonic acids (1‐substituted taurines) and 2‐substituted β ‐aminoethanesulfonic acids (2‐substituted taurines), are very important sulfur analogues of naturally occurring amino acids because α ‐aminoalkanesulfonic acids and their derivatives are unstable. Recently, we reported the efficient synthesis of 2‐substituted taurines,6 1‐substituted and cyclic taurines 7. Mass spectrometric (MS) fragmentations of N ‐butyloxycarbonyl‐ and benzyloxycarbonyl‐protected amino acids under fast‐atom bombardment (FAB) conditions were investigated 8, 9.…”

“…N ‐Benzyloxycarbonyl‐protected 1‐substituted and cyclic taurines were prepared by the method described in the literature 7. The ESI mass spectra of compounds 1 – 6 were acquired using a Bruker ESQUIRE‐LC™ ESI ion trap spectrometer (Bruker, Fallanden, Switzerland) equipped with a gas nebulizer probe, capable of analyzing ions up to m/z 6000.…”

Potential peptidic proteasome inhibitors by incorporation of an electrophilic trap based on amino acid derived α-substituted sulfonyl fluorides

“…19 After reduction with in situ prepared LiBH4, bromo-alcohols 4a and 4b were obtained in acceptable yields. Next, epoxides 5a and 5b were prepared with inversion of configuration by treatment with base (Cs2CO3), 20 which were immediately ring-opened by aqueous ammonia, 21 followed by protection of the amine with a Cbz-group 22 affording 7a and 7b in good (over 3 steps) yields of 64 and 80%, respectively. Alanine derived Cbz-protected amino alcohol 7c was obtained upon protection of the commercially available (R)-1-amino-2-propanol.…”