Degradation by ozonolysis

The viabihty of this synthetic approach to the introduction of a carboxylic acid fimction at C2 has been demonstrated in two ways. Following lithium diphenylcuprate addition to 564, the newly introduced phenyl group is subsequently degraded by ozonolysis to provide 567. Alternatively, reaction of 564 with diethylaluminium cyanide in toluene gives 568 which is also conveniently transformed into 567... 

Complete synthesis and systematic degradation by ozonolysis were performed when necessary. The hydrocarbons listed in Table I have been prepared. 

The starting material is ergocalciferol, the triene system and alcohol group of which are protected as a sulfur dioxide adduct and a silyl ether, respectively. The side-chain is degraded by ozonolysis at -10 °C in dichloromethane. Direct reduction with sodium borohydride destroys the ozonide and reduces the aldehyde to the alcohol. The yield amounts to 87 %. 

The methyl ester of 288, treated with phenylmagnesium bromide, followed by ( (3)-reacetylation and dehydration of the tertiary hydroxy group of the resulting diphenylcarbinol, afforded compound 293, which was degraded by ozonolysis to the nor-acid 294 (275). 

Branched-chain amino acids as precursurs of plant isoprenoids L-Leucine and L-valine, when fed to germinating pea seeds (Pisum sativum) were incorporated into squalene and 6-amyrin [39]. Chemical degradation by ozonolysis of the radioactive squalene revealed an equal distribution of the radioactivity in the IPP-derived (4 portions per molecule) and the DMAPP-derived moieties (2 portions per molecule). However, an unbalanced distribution in favor of the DMAPP-derived moiety of monoterpenoids was found after feeding radioisotopically labeled L-leucine, L-valine, DL-alanine, acetate, and R,S-MVA to intact plants of Cinnamomum camphora and of Pelargonium roseum [40]. The relatively low incorporation of amino acids was explained by several hypotheses a) the radioactivity of amino acids is scattered into other metabolites rather than monoterpenoids b) there is a great pool of the amino acids which leads to dilution of radioactivity, and c) the low permeation of the amino acids into the biosynthetic site of monoterpenoids [40]. The DMAPP-derived moiety of monoterpenoids, biosynthesized from [U- C]leucine and [U- ]valine was labeled with more than 64% of the incorporated tracers, while this moiety when derived from [2- " C]MVA contained less than 32% of the tracers [40]. This lends support to the interpretation that both amino acids are incorporated not via MV A, but by an alternate route, e,g, a combination of the well known mammalian leucine degradation pathway and a reversal of the MVA shunt (see below). The distribution pattern in monoterpenoids after administration of [2- ]alanine was similar to that after incorporation of MVA, which indicates that alanine is first metabolized to acetyl-CoA, which then constructs preferentially the IPP-derived moiety of the monoterpenoids via MVA [40]. 

The degradation of a 20-ketopregnane to a l7-ketoandrostane by ozonolysis first requires conversion of the 20-ketone to a A -oIefinic derivative. This can be accomplished by ... 

Ebdon and coworkers22 "232 have reported telechelic synthesis by a process that involves copolymerizing butadiene or acetylene derivatives to form polymers with internal unsaturation. Ozonolysis of these polymers yields di-end functional polymers. The a,o>dicarboxy1ic acid telechelic was prepared from poly(S-s tot-B) (Scheme 7.19). Precautions were necessary to stop degradation of the PS chains during ozonolysis. 28 The presence of pendant carboxylic acid groups, formed by ozonolysis of 1,2-diene units, was not reported. 

Degradation of bicyclic p-lactams has been used as a route to the monocyclic system. Highly functionalised P-lactams have been obtained in good yield by ozonolysis of A -cephems <96T10205> and enantiomerically pure 4-hydroxymethylazetidin-2-ones have been produced by degradation of a bicyclic oxazolidine, though in poor to moderate yield <96JCS(P1)227>. 

Major efforts to determine the structures of the optically active alkaloids were made with cryptaustoline iodide, and preliminary examination showed that the molecular formula could be expressed as CjgHjj(OH)(OCH3)3(NCH3)" I . Products obtained after Hofmann degradation and ozonolysis were identical with compounds obtained earlier by Robinson and Schopf from racemic 14, and the structure as one of the optical isomers of O-methylcryptaustoline iodide was established. 

While die above reactions will provide carboxylic acid products, each has problems associated with it. The cleavage of olefins to carboxylic acids [reaction (7.1)] can be carried out using potassium permanganate or by ozonolysis at low temperature followed by oxidative workup with hydrogen peroxide. Neither of diese mediods is very useful since only symmetric olefins provide a single carboxylic acid product. Unsymmetrical olefins give a mixture of two acids which must be separated. Furthermore the most useful synthetic processes are those which build up structures, whereas these reactions are degradative in nature. 

Degradation of the sterol stigmasterol to progesterone is achieved by the sequence shown in Figure 5.120. The double bond in the side-chain allows cleavage by ozonolysis, and the resultant aldehyde is chain shortened via formation of an enamine with piperidine. This can be selectively oxidized to progesterone. In this sequence, the ring A transformations are carried out as the... 

The reactivity of unsaturations with ozone has been applied to produce structures which allow subsequent degradation of materials by ozonolysis. In this way, Peters et al. [105] prepared polyurethanes using novel unsaturated diisocyanates which can be degraded by oxidative cleavage of the double bonds. 

The absolute configuration of lyngbyatoxin A (105 = teleocidin A-l) and teleocidin A-2 (106), potent tumor promoters isolated from the blue-green alga Lyngbya majuscula or terrestrial Streptomyces mediocidicus, was determined to be (14/ ) and (145), respectively, by chemical degradation including ozonolysis (103). 

Several reports of the effects of ozone in vivo are presented in Table XII. It is impossible to decide whether the effects of ozone are primary reactions or the result of a series of reactions initiated by ozone. All results can be rationalized as enzyme inhibition of one sort or another. Effects on membrane structure are harder to observe, and in one case it was reported that the malonaldehyde which would be expected on fatty acid ozonolysis was only observed after symptoms were apparent (74). Results of electron microscope examination showed that the first observable damage was in the stroma of the chloroplasts (70). One can easily argue that earlier damage could not be detected by microscopic techniques. However, recent reports that the chloroplast polyribosomes are much more susceptible to degradation by ozone are important observations which are consistent with the microscopy experiments (76). Chloroplast polysomes are also more susceptible to sulfhydryl reagents than are cytoplasmic polysomes (77). This evidence indicates that ozone itself, or a toxic product from primary oxidation, can pass through the cytoplasm and have its effect in the chloroplast. 

The four related compounds oxalomycin (157), neooxalomycin (158), cur-romycin A (159), and curromycin B (160) were reported in 1985 157 and 158 were isolated from a yet to be identified Streptomyces species (79, 80) and 159 and 160 from an ethidium bromide-treated strain of S. hygroscopicus (81, 82). The absolute configuration of oxalomycin (157) and neooxalomycin (158) has been determined by application of a combination of X-ray crystallography and chemical correlation to degradation products, the important derivatives being the p-bromobenzoate 161, obtained from 157 by ozonolysis-reduction, acetylation, partial hydrolysis, and reacylation with p-bromobenzoyl chloride, and the erythro acetate 162 which was obtained along with the threo compound 163 after acetylation of the ozonolysis products of 157 (79, 80). No stereochemical infor-... 

Another important result was obtained from in vivo experiments using the cabbage looper moth (CL), Trichoplusia ni (11). The biosynthetic pathway postulated for this insect is given in Fig 2. Substrates were applied to the gland and the (Z)-7-dodecenyl acetate isolated, cleaved at the double bond by ozonolysis, and the products isolated as benzyloximes. When acetate was used as substrate, radioactivity appeared in both products, but when hexadecanoic acid tritiated at the 16 position was used, radioactivity only appeared in the fragment derived from the terminal carbons. This demonstrated that incorporation took place as proposed in Fig 2, not by some scheme involving degradation and resynthesis. 

Sawada T, Motoi M, Nakamura Y (1989) Formation of organic acids from lignin by ozonolysis and biological degradation AIChE For Prod Div Sess 1988 143-147... 

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