D-Alanine derivatives

The co-polymerization of D-alanine-derived A-propargylamide 22, L-valine-derived 23, and pyrene-based monomer 24 gives helical poly(22 -< o-23-c -24) carrying pyrene. The secondary structure of the co-polymer is tunable by the composition of the optically active amino acid units and solvent, which makes it possible to control the direction of the pyrene groups in the side chain. The interaction between the pyrene groups is small when the co-polymer takes a helical structure. The pyrene groups are regularly positioned in the polymer side chain. The co-polymer emits weak... 

The scarcity of unnatural D-amino acids makes these compounds attractive synthetic targets, especially when one considers the disparity of price relative to their naturally occurring partners. If the hydroxyl group of an L-lactate could be displaced by a nitrogen nucleophile with inversion of configuration, this would allow easy access to D-alanine derivatives. Such a transformation can be realized by the reaction of 2 with diphenyl phosphorylazide and DBU to produce the (R)-azidoester 96 (98% ee) [33]. The initial step of the reaction is the formation of phosphonate 95. The resulting liberated azide then completely displaces the phosphonate group, with nearly total inversion of the stereo center. 

Fortunately, a host of methods is available for achieving this goal. They include resolution of a D,L-mixture [238] inversion of L-lactic acid derivatives (see Sections 1.2.1.2 and 1.2.2.2) asymmetric reduction of pyruvates catalytically [239], enzymatically [240], or with chiral boranes [241] and diazotization of D-alanine derivatives, which proceeds with net retention of configuration [242,243]. In addition, D-lactic acid can be obtained by the fermentation of glucose with Lactobacillus leichmannii in the presence of calcium carbonate [244],... 

The interesting TBS-protected acid chloride 310, available from monoester 23a by dual silylation of the hydroxyl and ester groups followed by treatment with oxalyl chloride, is an important intermediate in the synthesis of a key fragment (312) of rhisobactin (314), a microbial siderophore (Scheme 42) [92]. Completion of the synthesis of 314 is accomplished by reductive amination of 312 with D-alanine-derived aldehyde 313 followed by hydrolysis of the methyl esters and hydrogenolysis of the Cbz protecting group. 

Carbocyclic nucleoside precursor 154 was synthesized in 36% overall yield from an iV-hydroxy-D-alanine derivative by a reaction pathway involving oxidation, hetero-Diels-Alder cycloadditon of the nitroso intermediate to cyclopen-tadiene to give a chiral 1,2-oxazine, syn-dihydroxylation, and reductive cleavage. 

In comparison, a standard Mitsunobu reaction between 5-ethyl lactate and phthalimide gave a 45% yield of the expected protected D-alanine derivative with an ee greater than 99%, while Barrett s modified method using potassium phthalimide and an imidate ester gave a 25% yield with racemization. (Note Less than complete inversion of configuration has been noted with the use of 7 as a Mitsunobu-type reagent. )... 

D-cysteine (derivatives) 3-chloro-DL-alanine + iNaHS 3-chloro-D-Ala dehydrochlorinase or Pseudomonas putidaE. coli etc ... 

A further modification is a single (3-lactam ring as found in the mon-obactams. Characteristically, there is a sulfonate residue (derived from sulfate) on the nitrogen atom. An example is sulfazecin 8 from Pseudomonas acidophila and P. mesoacidophila. This material also contains a dipeptide unit of D-glutamate and D-alanine (Scheme 2). Pharmaceutical chemists have synthesized many variations on the (3-lactam structure and have devised semisynthetic processes. The resulting materials are not natural products and are beyond the scope of this article. 

Purification of some enzymes participating in the biosynthesis of glycopeptide cell-wall precursors has also been achieved. Examples include preparation of the enzymes necessary for synthesis of the enol ether 38 (see Section 11,6, p. 328),152-153-450 reduction of the enol ether to the muramic acid derivative,152-450,451 and the addition to the latter of amino acids452-456 or the dipeptide D-alanyl-D-alanine.160-457-458... 

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