First and Convergent Synthesis of Hybrid Sulfonophosphinopeptides

Abstract

Hybrid sulfonophosphinopeptides were first and convergently synthesized in satisfactory to good yields via the Mannich-type reaction of N-protected 2-aminoalkanesulfonamides, aromatic aldehydes, and aryldichlorophosphines and subsequent aminolysis with amino esters.

Facile synthesis of hybrid sulfonophosphinodipeptides composing of taurines and 1-aminoalkylphosphinic acids

“…The reaction of (S)-2-Benzyloxycarbonylamino-3-methylbutanesulfonamide (1d), benzaldehyde, and phenyldichlorophosphine was selected as an example to illustrate the reaction mechanism and diastereoselectivity. The sulfonamide, benzaldehyde, and phenyldichlorophosphine react to produce an N-sulfonylimine and phenylchlorophosphonous acid similar to previous reports (Li et al 2007;He et al 2009). The phenylchlorophosphonous acid then attacks the imine favorably from its Re side due to the existence of steric isopropyl group, and subsequent proton transfer affords the key intermediate as the N-sulfonylaminoalkylphosphinic chloride, which undergoes hydrolysis to generate the product hybrid sulfonophosphinodipeptide (S,S)-3g with S,S configuration as major product.…”

“…After aminolysis with ammonia, 2-(N-benzoxycarbonylamino)ethanesulfonamide (1a) was obtained according to the reported method (He et al 2009). It was used as an amine component in the Mannich-type reaction with benzaldehyde, phenyldichlorophosphine in anhydrous acetonitrile, and subsequent hydrolysis with water to afford a hybrid sulfonophosphinodipeptide 3a in a good yield ( Table 1, entry 1).…”

“…Aminoalkanesulfonic acids were prepared synthesized from vicinal amino alcohols according to our reported method (Zhang et al 2008). 2-Benzyloxycarbonylaminoalkanesulfonic acids were prepared from benzyl chloroformate and 2-aminoalkanesulfonic acids according to our reported method (He et al 2009). Acetonitrile was refluxed with calcium hydride and freshly distilled prior to use.…”

“…Phosphonopeptides, including phosphonamidate and phosphinamidate linkages, have been synthesized generally via the reaction of phosphonochloridates with amino acid esters or peptide esters (Kafarski and Lejczak 2000a), via the direct condensation of phosphonate monoesters with amino acid esters or peptide esters in the presence of coupling reagents (Galeotti et al 1996;Campbell and Bermak 1994a, b;Karanewsky and Badia 1986), and via our Mannich-type condensation of benzyl carbamate, aldehydes, alkyl dichlorophosphite, and subsequent aminolysis with amino esters (Fu et al 2006), or of N-Cbz protected amino amides/peptide amides, aldehydes, aryldichlorophosphines, and subsequent aminolysis with amino acid esters/peptide esters (Li et al 2007;He et al 2009). …”

“…Recently, we reported novel methods for the preparation of a-aminoalkylphosphonic acid derivatives via the phosphorusMannich-type reactions of carbamates, aldehydes, and chlorophosphites (Xu andFu 2000, 2001;Xu and Wei 2001;Liu and Xu 2005;Xu and Gao 2005;Liu et al 2006). We also prepared phosphinopeptides via the Mannich-type condensation of N-Cbz protected amino amides/peptide amides, aldehydes, aryldichlorophosphines, and subsequent aminolysis with amino acid esters/peptide esters (Li et al 2007) and sulfonophosphinopeptides via the Mannich-type condensation of N-Cbz protected amino alkanesulfonamides, aldehydes, aryldichlorophosphines, and subsequent aminolysis with amino acid esters/peptide esters (He et al 2009). The method has been applied to synthesize phosphinopeptides containing C-terminal a-aminoalkylphosphinic acids via the Mannich reaction and subsequent hydrolysis (Meng and Xu 2010).…”