Studies on Steroids. III. The Preparation of Steroid-21-yl-glucopyranosiduronamides.

Synthesis of C-21 glucosiduronates of cortisone and related corticosteroids

“…The material crystallized nicely from ethanol and from acetone-isooctane: [a]D + 87 ± 2 and +86 ± 2°( CHC1;) on different preparations and MD +590; lit. [a]D +121°(CHC13) (Wotiz et al, 1959), +103°( CHCI3) (Zorbach and Valiaveedan, 1964) and +95°( EtOH) (Nitta et al, 1964); \™fxH 238 µ (e 16,000); 3550, 1760, 1670, 1625, 1235, 1045, 979, 892, 863, and 787 cm-*; 0.64 (C-18 methyl), 1.41 (C-19 methyl), 2.01 (two acetoxyls), 2.10 (one acetoxyl), 3.78 (one methoxyl), 3.81-5.40 (protons adjacent to oxygen), 5.72 (C-4 olefinic proton), 4.15, 4.46, 4.69, 4.99 (7=18 cps) (C-20 methylene), 4.60, and 4.72 ppm (7=7 cps) (axial 1-proton of glucosiduronyl moiety).…”

“…On crystallization from methanol-water, the following was observed: yield 36%; mp 115-117°, [a]D +38 ± 2°( CHC13), XC£°H 241 µ (e 16,700); lit. mp 134-136°, [a]D +48 ± 4°( EtOH), XE¿°xH 242 µ (e 10,400) (Nitta et al" 1964); 3500, 1760, 1675, 1620 (s), 1220 (w), 1040 (w), 978 (s), 888 (w), and 782 (w) cm-1. (For chromatographically pure Ic, [a]D +126 ± 2°( EtOH); this value is used for calculating MD of lie in Table I.…”

“…A more recent paper by Nitta and Ide (1965) confirmed these findings. When Nitta et al (1964) prepared Ila-c, they interpreted the infrared spectra of these conjugates in terms of the foregoing findings and assigned the ß configuration to the glycosidic linkage of these compounds. Furthermore, the infrared spectra which we determined on glucosiduronates Ila-f do not have absorption bands at 1150 or 940 cm-1.…”

“…The molecular rotations of the a and ß anomers of each of the glucosiduronates (Ila-f) may be calculated by adding the molecular rotations of their component parts in the manner described by Klyne (1950) and utilized subsequently by Zorbach (1958) and by Nitta et al (1964) for steroidal glucosiduronates. Comparison of the molecular rotation found for each of the synthetic glucosiduronates (Ila-f) with that calculated for its a and ß anomers provides a good basis for assigning configuration to the anomeric center of each synthetic conjugate.…”

“…3 The conditions described in the Experimental Section for removal of the acetyl groups from Ila-f, substances in which the glucosiduronate moiety is attached to C-21, are too mild for complete removal of the acetyl groups from 3a-hydroxy-5/3pregnanes which have the glucosiduronate group attached at C-3 (V. R. Mattox and W. D, Vrieze, unpublished data). 4 The amides corresponding to IVa-c have been prepared by Nitta et al, (1964).…”