Betulinic acid, oxidation

Enhancement of the inhibitory activity was found in 3-oxo derivatives of 142 and 210, while either loss of oxygen functionality at C-3 of 210 or oxidation at C-3 of 147 led to the reduction of the activity [22]. Two 3-O-acetyl oleananes, 3-O-acetylerythrodiol (117 68% inhibition at lxlO3 mol ratio compound/TPA 80% cell viability) and acetyloleanolic acid (119 64% inhibition 80% viability), showed remarkable inhibitory effects with preserved higher viabilities of Raji cells than their free alcohols, erythrodiol (130 81% inhibition 50% viability) and 142 (70% inhibition 60% viability) [72]. Under the same assay conditions, betulinic acid (257) exhibited complete inhibition of activation with 80% cell viability [72]. Arjunolic acid triacetate (154 66% inhibition at lxl02 mol ratio compound/TPA) and arjunolic acid triacetate methylester (155 73%)... 

Degradative studies have shown that mercuric acetate oxidation of acetyl-betulinic acid (154) and dihydroceanothic acid (153) results in the formation of the C-28 — C-19 lactones (155) and (152) respectively. The configuration of the hydrogen at C-18 in these compounds is a. Under similar conditions betulin (156) is transformed into the ether (157). The product of mercuric acetate oxidation of lupenyl acetate (158) is 3j5-acetoxylupa-18,20(29)-diene (159) and not the I3(18),20(29)-diene as previously suggested. Treatment of the ring a seco-... 

In a similar study of the ozonolysis of betulin diacetate, Vystrcil and Budesinsky obtained inter alia compounds (168), (169), and (170). Continuing their studies of epimerisation at C-19 in the lupane series, these authors have reported the formation of the lactone (171) by acid equilibration of the bisnor-acid (172). Performic acid oxidation of the isopropenyl group in a number of lupene derivatives has been described. Most of the products can be rationalised by assuming the rearrangement of an initially formed epoxide. 

Several papers have appeared which provide further evidence for the course of the mercuric acetate oxidation of lupane derivatives (see Vol. 1, p. 186). The norketolactone (116), derived from the mercuric acetate oxidation product of acetyl betulinic acid, undergoes a ring E-homo rearrangement to (117) on treatment with t-butoxide. 

Steroids (Cjq) with four Cg q cles and one Cg cycle E, which are derived from the hydrocarbon lupane, are lupeol (3-96) and a product of its oxidation on C-28 known as betulinic acid (3-97). CjQ Steroids also occur with hve Cg cycles. The most important of these compounds are a-amyrin (3-98), derived from the hydrocarbon ursane, and P-amyrin (3-99), which is derived from the... 

Several studies have been devoted to the one-step oxidative conversion of betu-lin to betulinic acid with selected strains of fxmgal microorganisms [29-31], as well to the microbial conversion of betulin or betulinic acid to their 3-oxo coxmterparts (betu-lone or betulonic acid, respectively) [27,32-34]. 

By using betulin as substrate, some mechanistic studies were performed and it was demonstrated that these reactions are catalyzed by Brpnsted acid species generated in situ from the hydrolysis of Bi(0Tf)3-.vH20. This process was also applied to other terpenic compounds. The sesquiterpene ( )-caryophyllene oxide originated clov-2-en-9a-ol by a cariophyllene-clovane rearrangement (Scheme 41) whereas 3-oxo- l 8a-olean-28- l 3(3-olide was obtained from oleanonic acid (Scheme 42). With this triterpene derivative, only 28,13(3-lactonization occurred, with inversion of the configuration of the stereocenter at C18 [133],... 

Catalytic hydrogenation of the diene (96), from mercuric acetate oxidation of betulin diacetate, yielded (97) and (98). The latter was further reduced to the 18/3H,19/8-lupane (99).70 Isomerization of betulin diacetate with hydrobromic acid in acetic acid-acetic anhydride afforded (97), instead of the usual products with ring E enlarged.71 Glochidone (100) is readily prepared from lupen-3-one by oxidation with 2,3-dichloro-5,6-dicyanobenzoquinone.72 73... 

Carotene was often used as model drug, but data on real drugs like hydrocortisone, paclitaxel, betulin and their derivatives have also been published poly(styrene)-fo-poly(ethylene oxide) (PS-fo-PEO), poly(butilacrylate)-fo-poly(acrilic acid), poly(ethylene glycol)-fo-poly(lactic acid) (PEG-fo-PLA) and PEG-fo-poly(lactic-co-glycolic acid), with different molecular weight, are some of the block copolymers employed by the authors. 

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