Epimers direction

In an effort to make productive use of the undesired C-13 epimer, 100-/ , a process was developed to convert it into the desired isomer 100. To this end, reaction of the lactone enolate derived from 100-) with phenylselenenyl bromide produces an a-selenated lactone which can subsequently be converted to a,) -unsaturated lactone 148 through oxidative syn elimination (91 % overall yield). Interestingly, when 148 is treated sequentially with lithium bis(trimethylsilyl)amide and methanol, the double bond of the unsaturated lactone is shifted, the lactone ring is cleaved, and ) ,y-unsaturated methyl ester alcohol 149 is formed in 94% yield. In light of the constitution of compound 149, we were hopeful that a hydroxyl-directed hydrogenation52 of the trisubstituted double bond might proceed diastereoselectively in the desired direction In the event, however, hydrogenation of 149 in the presence of [Ir(COD)(py)P(Cy)3](PF6)53 produces an equimolar mixture of C-13 epimers in 80 % yield. Sequential methyl ester saponification and lactonization reactions then furnish a separable 1 1 mixture of lactones 100 and 100-) (72% overall yield from 149). 

Conversion of the resulting separate D-seco D-E trans i-vincadiffor-mine diols 198-201 to their primary tosylates and tertiary trimethylsilyl-oxy derivatives 202-205 and coupling to vindoline by the chlorination-silver tetrafluoroborate-potassium borohydride sequence provided amino tosylates 206-209, which could be directly subjected to cyclization or, alternatively, converted to the C-20 -C-21 epoxides 178, 181, 210, and 211 by reaction with tetrabutylammonium fluoride (Scheme 53). While cyclization of the tosylates 206-209 led essentially only to quaternary salts which could be debenzylated to provide the lower energy atropi-somer of vinblastine (1), leurosidine (56), vincovaline (184), and its C-20 epimer (212) respectively, cyclization of the epoxides 178, 181, 210, and... 

Hartman and R. Barker synthesized 1,4-anhydroerythritol (3) by the saponification of 1-O-p-tolylsulfonyl-D-erythritol (1). The reaction apparently proceeded by direct reaction of the 4-hydroxyl group with the 1-p-tolylsulfonoxy group, and not through the intermediate formation of the 1,2-anhydride, which would have afforded the epimer, namely, 1,4-anhydro-D-threitol (2). Similarly, 1-O-p-tolylsulfonyl-D-threitol gave 1,4-anhydro-D-threitol (2). 

The mixture of the crude product hydrazone 138 and the excess of hydrazone 129 was used directly in an acidic acetalization reaction utilizing aqueous 3n HCl in a biphasic system and gave a diastereomeric mixture of sordidin (126) and 7-epi-sordidin (7-epi-126) in 84% yield over two steps in a 1.5 1 ratio. Gratifyingly, we succeeded in separating the desired sordidin epimers by preparative gas chromatography. As a result, both could be obtained in diasteromerically pure form (sordidin de > 99% 7-epi-sordidin de > 97%) and with a high enantiomeric excess for each epimer (ee > 98%). 

UDP-Gal 4-epimerase16 161 (Eq. 20-1, step c see also Eq. 15-13 and accompanying discussion). Absence of this enzyme also causes galactosemia.11 The overall effect of the reactions of Eq. 20-1 is to transform galactose into glucose 1 -P. At the same time, the 4-epimer-ase can operate in the reverse direction to convert UDP-glucose to UDP-galactose, when the latter is needed for biosynthesis (Fig. 20-1). 

If the observed order of priority of the remaining three functions ( b > c) is in a clockwise direction, the absolute configuration is designated R (rectus or right) if counterclockwise, fixe configuration is S (sinister or left). Diasteteomers which differ at a single stereocentei are called epimers. 

Hydrogen transfer assumes a particularly important role in the photochemistry of 20-ketosteroids because it provides a direct method of attack on the C-18 methyl group. Irradiation of 3,3-dimethoxy-20-oxo-pregnane (Formula 271) in methanol gives two isomers (C-20 epimers) of Formula 272 in 24-35% yield and 8-12% yield, respectively, plus the ketoolefin (Formula 273) and the diene (Formula 274) (112). 

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