Alkaline peroxide oxidation4 transformed IV into V (R = H) which was converted with diazomethane into the ester V (R = CHa), and cyclized with potassium t-butoxide in benzene. The resulting keto ester was decarbomethoxylated with hydrochloric and acetic acid to give the dl-ketone VI, m.p. 155.5-161.5". The infrared spectrum of this material was indistinguishable from that of authentic 3,B-hydroxy-9,1 l-dehydroandrostane-17one.g (S) A t this stage t h e 3-hydroxyl group was protected a s the tetra.(9) C. W. Shoppee, J . Ckem. SOC., 1134SOC., (1946). hydropyranyl ether (cf. ref. 3). Sir:The ability of aliphatic carbodiimides to form amide bonds in aqueous solution directly from the amine and carboxyl components under very mild conditions' suggested the use of these reagents for the cyclization of a pencilloic acid to a penicillin. We have Drepared by total synthesis in good overall yield the penicilloic acid corresponding to penicillin V (phenoxymethylpenicillin). By use of N ,N'dicyclohexylcarbodiimide cyclization was effected rapidly a t room temperature, thereby completing the first rational synthesis of a natural penicillin.2Condensation of D-penicillamine with t-butyl phthalimidomalonaldehydate afforded the t-butyl ~-a-4-carboxy-5,5-dimethyl-a-phthalimido-2-thiazolidineacetate (I), C2d&4N2O6S, m.p. 161" dec.
Sir :It was first noted by Ruzicka and van Melsen that treatment of bromonorcedrenedicarboxylic acid (bromoNCDA) with base leads to the loss of the elements of hydrobromic acid and carbon dioxide and the formation of an,unsaturated bicyclic monobasic acid, C12H1802.1 On the (incorrect) assumption that bromoNCDA is a bromosuccinic acid2 the reaction is unexceptional and has many precedents. It was eventually recognized however that the C12 acid is not an alp unsaturated acid and that apparently bromide ion and carbon dioxide are lost from the same carbon atom.'J Little further progress was made in the elucidation of the structure of the C12 acid, and the rearrangement which leads to it has remained one of the arcana of cedrene chemistry.* An entirely new light was shed on the reaction when it was demonstrated that NCDA is a glutaric acid derivativeP and the problem of the base decomposition of bromoNCDA was re-examined. It seemed to us likely that the reaction was essentially one of solvolysis of a neopentyl bromide type, undoubtedly facilitated in the present case by the cancellation of the positive charge on the relevant carboxyl group by formation of a carboxylate anion :The correctness of this assumption was proved in the following manner: The monomethyl ester of NCDA, m.p. 13loI2 was converted into the methyl ketone, dinitrophenylhydrazone m.p. 138' , by reaction of the acid chloride with dimethyl cadmium. Perbenzoic acid cleavage, followed by base hydrolysis of the resulting acetate gave the anticipated hydroxy acid ClSHzoOs, which was then heated with phosphorus tribromide. After hydrolysis with water a crystalline acid was obtained which infrared comparison showed to be identical with the C12 acid of Ruzicka and van Melsen.An attractive hypothesis was that the quaternary grouping involved in the rearrangement of bromo-NCDA included the gem dimethyl group of (1) L. Ruzicka and J. The last published investigation of the Ct; acid is by W. Treibs, Bet.. 7 6 , 160 (1943). (6) G. Stork and R. Brealow, THIS J O U R N A L , 76, 3291 (lQ58).cedrene.6 This hypothesis received support from our observation that the characteristic gem dimethyl split peak a t about 7.3 p,7 which is clearly evident in the infrared spectra of practically all the cedrene degradation products which we have examined, is changed to the usual C-methyl band in the rearranged Clz acid. Conclusive proof of the involvement of the gem dimethyl group was obtained by taking advantage of the fact that a rearranged acid in which the original gem dimethyl grouping had changed to two separate methyl groups must show between one and two more Cmethyls than the parent compound. Experimental results were in agreement with predictions : NCDA monomethyl ester showed C-methyl : Calcd. for one C-methyl, 6.4. Found: 5.9y0. The C12 acid showed C-methyl : Calcd. for three C-methyls, 23.2. Found: 22.6%.The rearrangement of bromonorcedrenedicarboxylic acid, which incidentally finds a striking parallel in the transformation of bromocamphoric acid into laurolenic acid...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.