An improved synthesis of taurine‐ and glycine‐conjugated bile acids

Abstract

A simple and efficient method for the synthesis of taurine- and glycine-conjugated bile acids is described. The condensation reaction was achieved by the simple mixing of unconjugated bile acid (1.0 eq.), taurine (2.0 eq.) (or glycinate ester), diethyl phosphorocyanidate (1.2 eq.) in the presence of triethylamine at room temperature for 30-60 min. Sample clean-up was effected by the use of a prepacked Sep-Pak C18 cartridge for reversed-phase solid extraction or by direct recrystallization, yielding the desired taurine and glycine conjugates in 89-93 and 92-96% isolated yields, respectively.

Chemical Synthesis of (22E)-3.ALPHA.,6.ALPHA.,7.ALPHA.,12.ALPHA.-Tetrahydroxy-5.BETA.-chol-22-en-24-oic Acid and Its N-Acylamidated Conjugates with Glycine or Taurine: Precursors of the [22,23-3H] Labelled Tracers

“…As expected, N-acylamidation of 1a with glycine methyl ester hydrochloride in the presence of diethyl phosphorocyanidate (DEPC) and triethylamine (Et 3 N) 17) as coupling reagents in N,N-dimethylformamide (DMF) under mild experimental conditions yielded the corresponding 24-glycine methyl ester derivative of 1a as the major product. The resulting methyl ester intermediate was hydrolyzed with NaOH.…”

Isolation and chemical synthesis of a major, novel biliary bile acid in the common wombat (Vombatus ursinus): 15α-hydroxylithocholic acid

“…Synthesis of the taurine and glycine conjugates of 15a-hydroxylithocholic acid N-Acylamidation of the C-24 carboxyl group in 1a with glycine methyl ester hydrochloride or freshly powdered taurine was effectively attained using diethyl phosphocyanide as a condensing reagent and triethylamine as a catalyst (27). After the condensation reaction, the resulting solutions were adjusted to appropriate pH with the treatment of acid and/or base (see Methods), and the desired glycine (1c) and taurine (1d) conjugates (as the sodium salts) were recovered efficiently by applying a reverse-phase prepacked cartridge (Sep-Pak Vac tC 18 ) for solid-phase extraction.…”

“…Bile acids are of two types: C 24 bile acids [with a C 5 (isopentanoic acid) side chain] and C 27 bile acids [with a C 8 (isooctanoic acid) side chain]. The C 24 and C 27 bile acids, together with C 27 bile alcohols, are the predominant chemical metabolites of cholesterol and are the major chemical form in which cholesterol is eliminated in most vertebrates (1). All primary C 24 bile acids have a hydroxyl group at position C-3 (from cholesterol) and at C-7, as cholesterol 7a-hydroxylation is the rate-limiting step in bile acid biosynthesis.…”

Chemical synthesis of (22E)-3α,6β,7β-trihydroxy-5β-chol-22-en-24-oic acid and its taurine and glycine conjugates

“…Condensation of the carboxyl group at C-24 in the ⌬ 22 -␤-MCA [1a] with the amino group of taurine (or of glycine methyl ester) was successfully attained by the use of DEPC as a coupling reagent and Et 3 N as a catalyst (23). The N-acylamidation reaction involves the formation of intermediary acyl phosphates as carboxylactivated intermediates by the interaction of carboxylic acid with DEPC in the presence of Et 3 N and subsequent coupling with amines to give the corresponding amides in one step.…”