Calcimycin Antibiotic

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

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. 

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... 

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

The interesting antibiotics X-14S47A and A-23187 (calcimycin) contain a novel 2-ketopyrrole moiety, which is apparently important for biological activity. Nicolaou has developed a simple method for incorporation of this unit into the sensitive intermediates required for preparation of the natural products. Through use of the Mukaiyama protocol, formation of the 2-pyridyl tldol ester was effected with 2,2 -di-pyridyl disulfide and triphenylphosj iine. The reaction mixture was then cooled to -78 °C and was treated with a solution of pyrroylmagnesium chloride in THF (equation 21). 

The antibiotic (-)-A-23187 (calcimycin) has been prepared by Boeckman using similar methodology (equation 23). No racemization was observed at the position a to the thiol ester. 

The antibiotic calcimycin (or A23187) is a widely used probe for calcium ion transport in biological systems. A synthesis of the core of this antibiotic has been developed [15]. Although little stereoselectivity is associated with this method it is rather remarkable in that two ring closures are involved, the first involving hemi-acetal formation and the second an electrophilic closure (Fig. 12). 

A quantitative 1,4-chirality transfer is observed in the construction of the acyclic segment C-l to C-ll 11 of the antibiotic ionophore A-23187 (12, calcimycin)441. Both the wanted and unwanted stereoisomer 9 and 10, obtained from the alcohol 8 by pyridinium chlorochromate oxidation followed by Grignard reaction with vinylmagnesium bromide, can be rearranged by the ester enolate procedure simply by changing the reaction conditions to give the stereoisomer 11 with the correct configuration at C-10. 

Painter. G.R. Pressman, B.C. Cation complexes of the monovalent and polyvalent carboxylic ionophores Lasalo-cid (X-537A). monensin, A23187 (calcimycin). and related antibiotics. Met. Ions Biol. Syst. 1985.19. 229-294. 

Cation Complexes of the Monovalent and Polyvalent Carboxylic lonophores Lasalocid (X-537A), Monensin, A-23187 (Calcimycin) and Related Antibiotics... 

A synthesis of the ionophore antibiotic A 23187 (calcimycin) has been completed, using D-glucose as a source of the enone (34), and... 

L-lsoleucine. A full account has been given of the synthesis of the spiroketal antibiotic A23187 (calcimycin) from glucose (see Vol. 18, p.250-1). Full details have also been reported for the synthesis of a glucose-derived fragment, mentioned last year (Vol. 19, p.256), corresponding to C(9)- C(14) of okadaic acid, and the total synthesis of the complete structure of this marine toxin has... 

Other natural products whose syntheses were reported during the period of this Report, and which are worthy of more than a cursory inspection, include the antibiotic A-23187 (calcimycin) (213), the ansa-macrocyclic lactam maytansinol (214), and the lignan steganone (215). ... 

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