Epimers

Epimers (Section 25 21) Diastereomers that differ in configu ration at only one of their stereogenic centers... 

The researchers investigated three MeBmt analogs the C-4 epimer ((45)-MeBmt), the C-4 des methyl analog (MeBth), and the C-4 dimethyl (MeBm2t) analog. The immunosuppressive activity of the analogs follows the order MeBmt > MeBm2t > MeBth > (4 )-MeBmt. 

An alternative route to 6a- uorosteroids was developed by treating the enol acetate (93) of a A -3-one with perchloryl fluoride ia aqueous dioxane to obtain a mixture of the 6-fluoro-epimers (94) which were converted iato the 6a-fluoro-A -3-ones (95) on treatment with. ... 

Diastereomers which differ at a single stereocenter are called epimers. 

Antineoplastic Drugs. Cyclophosphamide (193) produces antineoplastic effects (see Chemotherapeutics, anticancer) via biochemical conversion to a highly reactive phosphoramide mustard (194) it is chiral owing to the tetrahedral phosphoms atom. The therapeutic index of the (3)-(-)-cyclophosphamide [50-18-0] (193) is twice that of the (+)-enantiomer due to increased antitumor activity the enantiomers are equally toxic (139). The effectiveness of the DNA intercalator dmgs adriamycin [57-22-7] (195) and daunomycin [20830-81-3] (196) is affected by changes in stereochemistry within the aglycon portions of these compounds. Inversion of the carbohydrate C-1 stereocenter provides compounds without activity. The carbohydrate C-4 epimer of adriamycin, epimbicin [56420-45-2] is as potent as its parent molecule, but is significandy less toxic (139). 

The chemical syntheses of l,24(R),25-trihydroxy-vitamiQ [56142-94-0] and l,24(3),25-trihydroxy-vitamiQ D [56142-95-1] were reported (131,132) ki 1975. The chemical synthesis of 25,26-dihydroxy-vitamin [29261 -12-9] has also been described, and it has been determined that the biologically occurring epimer is 25(R),26-dihydroxy-vitamin (117,133—135). The 23,25-dihydroxy-24-oxo metabohte has been isolated (136) as well. 1 a-Hydroxycalcitroic acid (l-hydroxy-24-nor-9,10-secochola-5,7-10(19)-ttien-23-oic acid) [71204-89-2], 25-hydroxy-26,23-lactone vitamin [71203-34-6],... 

Modification of the Proline Fragment. Besides the 4 -ethyl analogue of lincomycin, co-produced in fermentations of S. lincolnensis (48), other 4 -alkyl analogues were chemically synthesized. A peak of activity is reached with the trans-4 and hexyl analogues (11), the cis-epimers (12) possessing about one-half of the activity of the trans-. Equivalent activities are shown by A/-ethyl hncosarninides, but larger A/-alkyl substituents show decreased activity (86). 

Scientists at Merck developed a cephalosporin synthesis based on the addition of azidoacetyl chloride to 1,3-thiazines (56). Although this gives the incorrect 7a -epimer (57), it could be equilibrated to a mixture of 7-amino epimers (see Section 5.10.3.3) from which the desired 7/3-isomer could be separated and further elaborated to cephalosporins (B-82MI51001). 

Scheme 15 shows an example of the cleavage of a carbon-sulfur bond by chlorinolysis. This reaction can also be carried out on the intact penam ring system as shown in Scheme 17 (71JA6269 and the previous paper). In Scheme 18 this reaction is used to form the epimer of... 

Epimerization at C(5) has not been observed under the conditions discussed for the preparation of C(6) epimers (see Section 5.11.3.8.4). It is possible to prepare 5 -epipenicillins, however, as shown in Scheme 28. Note particularly the successful removal of the phthaloyl group (step iii) in this sequence, a procedure which leads to /3-lactam cleavage when C(5) is the R, or natural, configuration. Silylation of (35) followed by DBN treatment afforded (36), which corresponds to epimerization at C(3), and (37), which corresponds to epimerization at C(3) and C(6). No product corresponding to only C(6) epimerization was observed (76JOC2561). 

The behavior of penicillins under hydrolysis conditions has been extensively studied e.g. B-49MI51102,71JPS503), and Some of the early work has been summarized in Section 5.11.3.2. Generally, the rate of /3-lactam hydrolysis for various penicillins reaches a minimum between pH 6 and 7, and increases sharply above and below that minimum (74CPB1186). Under basic conditions, hydrolysis rates are relatively insensitive to the 6-substituent, and the product is the relatively stable penicilloate and, at least in some cases, its 5-epimer (Scheme 51) (77JHC503). 

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