Carbon chain elongation

Oxidation and 2-Carbon Chain Elongation. In some cases, acyl-CoA conjugates formed from xenobiotic acids can also enter the physiological pathways of fatty acids catabolism or anabolism. A few examples are known of xenobiotic alkanoic and arylalkanoic... 

Of great importance for porphyrin chemistry is the introduction of carbon substituents by Vilsmeier formylation100 or Friedel-Crafts acylation.100 The introduced substituents allow further carbon-chain elongations and other transformations so that interesting porphyrin derivatives can be synthesized. The Vilsmeier formylation of copper octaethylporphyrin (5) takes place at themethine position. The copper can then be easily removed by treatment with acid.105... 

A multi-step reaction sequence was then realized to prepare the precursor (178) for the pivotal macrocyclization reaction. Alternate stepwise chain elongations were achieved according to Schemes 28 and 29. Reaction of the tosylate prepared from the alcohol 162 with lithium acetylide afforded the alkyne 174 (Scheme 28). Following the introduction of a tosylate at the upper branch, a one-carbon chain elongation of the terminal alkyne afforded the methyl alkynoate 175. A methyl cuprate 1,4-addition was used to construct the tri-substituted C double bond stereoselectively. For this purpose, the alkynoate 175 was initially transformed into the Z-configured a,/ -unsat-... 

This classification leaves out of account the other applications to a-amino acids (e.g., as chiral auxiliaries). Besides, the approach shown in Scheme 2 excludes higher carbon chain elongation (from C5 up to C16), which can be effectively realized using organo-metallic additions and Wittig-type reactions [e.g., see Ref 17]. 

Keeping the foregoing limitations in mind, we will discuss the recently published methods for achieving carbon chain elongation. Throughout this chapter, the syn—anti convention, as proposed Masamune et al. [18,19] will be followed. The use of the threo-erythro descriptors is restricted to sugars to avoid any ambiguity. 

The second procedure, Part B, Illustrates an easy synthesis of y-keto esters by "reductive succlnoylation" of a ketal function.5 It is useful not only for the preparation of keto esters, but also as a four-carbon chain-elongation reaction starting from ketones. The reaction is applicable to a diverse range of ketals as shown in Table II. The enol silyl ether... 

As was amply demonstrated in the preceding sections of this chapter, numerous C-C bond-forming reactions are applicable for the preparation of products with a terminal double bond. Thus the sequence (i) introduction of the terminal alkene moiety, (ii) isohypsic double bond transformation leading to the derivatives like 127 or 128, and (iii) the C-C bond-forming step, may be considered as a reliable operation for carbon chain elongation. 

Other Methods of One-Carbon Chain Elongation of Aldoses... 

An aminohomologation of carbaldehydes was developed by Dondoni and coworkers, thus remarkably extending the scope of their one-carbon chain-elongation method (Scheme 13.28). For example, the A-benzylnitrone 53, derived from D-glyceraldehyde acetonide (R)-24, was added to... 

Two-Carbon Chain Elongation of Aldehydes 13.5.5.1 Asymmetric Aldol Reactions... 

The biologically important 2-deoxypentoses can be prepared readily by the two-carbon chain elongation of 2,3- -isopropylidene-D-glyceraldehyde following Roush s allylation method (Scheme 13.54), relying on the highly diastereoselective additions of enantiomerically pure allylboronates derived from (R,R) and (5, 5 )-tartaric acid [100]. Similarly, the 2,6-dideoxyhexose derivative 155 was obtained by Roush and Straub (Scheme 13.54) [101]. 

The two-carbon chain elongation of protected D-glyceraldehyde (R)-24 and (R)-62 can be realized via ( -7-alkoxyallylboronate additions, followed by alkene ozonolysis. The allylboronate 162 generated in situ adds to (R)-62 giving a single stereoisomer 163, which can be converted to D-arabinose derivatives following ozonolysis (Scheme 13.57). Similarly, 164 added to (R)-24 gave a major adduct 165 that was then converted into 2-0-methyl-D-arabinose derivatives [105]. 

Three-Carbon Chain Elongations 13.5.6.1 Allylmetal Additions... 

Roush s three-carbon chain-elongation method applied to 2,3-O-cyclohexylidene-D-glyceralde-hyde (R)-62 is an efficient approach to D-glucitol derivatives, which relies on the vyfx-selective epoxidation of homoallylic alcohol 170 (Scheme 13.59) [105,107]. 

Most of the methods presented for the de novo synthesis of linear monosaccharides can be used to prepare branched-chain sugars and analogs and some examples are given above and below. The branched-chain aminolactone 222 was prepared by two-carbon chain elongation via addition of 221 to 2,3-0-isopropylidene-L-glyceraldehyde (Scheme 13.69) [126]. 

Several s)uitheses of aminodeoxypentoses have employed a similar approach in which a three-carbon starting material is condensed with a two-carbon entity [237]. A synthetic equivalent of the glycoaldehyde anion, the dioxaborole 98 (O Scheme 46) has been used for the carbon chain elongation of aldehydes. Thus L-ribose is prepared from the addition of... 

Two-carbon chain elongation of protected D-glyceraldebyde R)-37 and R)-99 can be realized via ( )-)/-alkoxyallylboronate additions, followed by alkene ozonolysis, furnishing D-arabi-nose derivatives [300]. 

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