Calcimycin

Calcia [1305-78-8] Calci-Bind Calcimar Calcimycin [52665-69-7] Calcination Calcined gypsum Calcined limestone... 

Pyrro/e ethers A23187 (calcimycin) [52665-69-7] Streptomyces chartreusis NRRL 3882 181-182 152 153... 

Antibiotic A-23187 (Calcimycin) Evans,7ACS, 1979, 707,6789. Grieco, 7ACS, 1982,104, 1436. Nakahara Si Ogawa,... 

Interestingly 1,4-addition product 21 is equipped with the same relative and absolute configuration of the four stereogenic centers found in the ionophore calcimycin. 

Claisen rearrangements of silyl ketene acetals have been used in numerous syntheses, including the synthesis of the ionophore antibiotic Calcimycin outlined in Figure Si3.12. 

The compounds calcimycin (A23187, 168) and nocobactin (187) contain the common feature of an oxazole ring but otherwise differ widely in functionality they are grouped together on the basis of their being cation ionophores. Calcimycin (A23187, 168) occurs in Streptomyces chartreusensis, from which it may be isolated as the mixed magnesium-calcium salt (89, 90). The structure of the free acid, a crystalline solid, was determined spectroscopically to be 168... 

Two formal total syntheses of calcimycin have been achieved (94-96). They are similar in concept in that the retrosynthetic analyses entail disconnection of the l,7-dioxaspiro[5.5]undecane moiety of 168 to the ketodiol precursor 170 which would readily yield calcimycin on acid-catalyzed cyclization (spiro-ketalization). Further retrosynthetic fragmentation of ketodiol 170 into the pyr-... 

In total synthesis of the structurally unique natural product calcimycin (15), Grieco and others used Ireland-Claisen rearrangement of the ester 17 to synthesize the key intermediate (18)7 (Scheme 1.3g). Monosilylation of the diol 16 followed by treatment with propionyl chloride in pyridine gave rise to the ester 17 in 90% yield. Treatment of 17 with LDA in THF at —78 C, subsequent addition of ferf-butyldimethylsilyl chloride in HMPA, and brief heating of the resulting silylketene acetal provided the corresponding silyl ester. Subsequent hydrolysis of the silyl ester and esterification with diazomethane gave 18 in 90% yield from 17. 

COX-1 Assay Macrophages were incubated with test compound at different concentrations or solvent (Me2SO) for 1 h and were stimulated with calcimycin 1 pmol/1 for 1 h. The amount of 6-keto-PGFia (a stable metabolite of PGI2) in supernatants was measured by RIA according to manufacturer s guide. The inhibitory ratio was calculated as... 

Cs, Ct, Cc refer to 6-keto-PGFia concentration in supernatants of calcimycin, test compound, and control groups, respectively. 

Another useful system is o-nitrophenyl selenocyanate and tributylphos-phine (Bu3P), developed by Grieco and co-workers,104-106 which has been employed in the synthesis of intermediates leading to the ionophone antibiotic calcimycin.103... 

As illustrated in Scheme 11.10, enone 32, prepared from D-glucal in a multistep sequence, was reacted with lithium dimethylcuprate. Clean axial attack of the reagent at C4 gave the substituted ketone 33. Subsequent Wittig methylation and reduction was used to introduce the second methyl group of 34, a key intermediate in the synthesis of a-multistriatin. The same sequence was used in the preparation of calcimycin (A23187), the 4-C-methyl synthon 33 being used to construct the two required chirons [50]. 

Nakahara, Y, Fujita, A, Beppu, K, Ogawa, T, Total s3mthesis of antibiotic A23187 (calcimycin) from D-glucose, Tetrahedron, 42, 6465-6476, 1986. 

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