Bisquaternary ammonium salts derived from 3α,12α-Diamino-5β-cholane and 3α,12α-Diamino-24-nor-5β-cholane

Abstract

The preparation of 3α,12α-bisdimethylamino-5β-cholane dimethiodide, 3α,12α-bisdimethylamino-5β-cholane dimethiodide, 3α,12α- bisdimethylamino-24-nor-5β-cholanedimethiodide, and 3α,12α- bisdimethylamino-24-nor-5β-cholanediethiodide, from deoxycholic acid are described. During this work it was found that attempted copper- quinoline decarboxylation of dehydrocholic acid gives rise to lactol formation, and that what had previously been considered to be 3α,12α- dihydroxy-5β-cholane is a mixture of this compound and 12α,24- dihydroxy-5β-cholane. Comparable selectivity of attack by methanesulphonyl chloride and toluene-p-sulphonyl chloride occurs with various polyhydric alcohols derived from bile acids, as evidenced from the products of reduction of the sulphonates with lithium aluminium hydride. With both 5α- and 5β-cholane derivatives, a C 3 equatorial hydroxyl group exhibits comparable reactivity to the terminal primary hydroxyl group, generated from the bile acid carboxylic group, towards both sulphonyl chlorides. With axial hydroxyl groups at C 7 and C 12, toluene-p-sulphonate formation is much more difficult than methane- sulphonate formation. Reduction by means of lithium aluminium hydride of equatorial sulphonate esters at C 7 and C 12 gives rise to a methylene group, but the axial sulphonates under the same conditions give the axial alcohol. The same clear distinction between equatorial and axial sulphonate esters is not observed at C 3 and C 6, but 17α- methanesulphonyloxy-5α-androstane gives 5α-androstane and the 17β- ester gives 17β-hydroxy-5α-androstane. Reduction of 12-oximino groups in both 5α- and 5β-cholanes with sodium and ethanol, hydrogen in the presence of a catalyst, or lithium aluminium hydride gives solely the 12α-amino compound.

Properties of Hydrogels Derived from Cationic Analogues of Bile Acid: Remarkably Distinct Flowing Characteristics

“…26 Deoxycholic acid 1 is converted to its diformyl derivative 2 (90%) by heating with formic acid at 50 °C. 27 A Hunsdiecker type reaction of 2 with Pb(OAc) 4 and iodine in CCl 4 gives the 24-nor-23-iodo derivative 3 (65%), 28 which is deformylated (K 2 CO 3 /MeOH) to obtain 4 (95%). Reaction of 4 with N-methylmorpholine, N-methylpiperidine, and 1,4-diazabicyclo[2,2,2]octane (DABCO) in refluxing MeCN yielded salts NMM-DC, NMP-DC, and DABCO-DC, respectively.…”

Novel Cationic and Neutral Analogues of Bile Acids: Synthesis and Preliminary Study of Their Aggregation Properties

“…The synthesis of 1 − 3 is outlined in Scheme . Deoxycholic acid 7 was converted to its diformyl derivative 8 , which was transformed to the 24- nor -23-iodo derivative 9 with Pb(OAc) 4 and iodine in a Hunsdiecker type reaction . Deformylation (K 2 CO 3 /MeOH) followed by reflux with N -methylmorpholine, pyridine, or triethylamine in MeCN yielded salts 1 , 2 , and 3 , respectively, which were crystallized from water .…”

Imprinted Polymers as Protecting Groups for Regioselective Modification of Polyfunctional Substrates

“…The product was shown by TLC to contain a small amount of starting material and two faster-moving components. Column chromatography (silica gel, elution with ethyl acetate) yielded the desired compound (2.87 g, 75%) as colorless needles:mp 148−152 °C (lit . mp 150 °C).…”