126629-10-5Relevant academic research and scientific papers
Synthesis and X-ray crystal structure of (-)-calicheamicinone
Clive, Derrick L. J.,Bo, Yunxin,Selvakumar, Natesan,McDonald, Robert,Santarsiero, Bernard D.
, p. 3277 - 3290 (2007/10/03)
Diels-Alder reaction between ketene acetal 3 and the β-nitroacrylate ester 12 of (-)-8-phenylmenthol gave optically pure ketone 17. This substance was modified in such a way as to remove the chiral auxiliary and afford the epimeric silyl ethers 20M and 20m. Following procedures worked out using racemic materials, both 20M and 20m were converted into optically pure (-)- calicheamicinone (1). This is a crystalline substance, and an X-ray structure determination was carried out.
Synthesis of (±)-calicheamicinone by two methods
Clive, Derrick L.J.,Bo, Yunxin,Tao, Yong,Daigneault, Sylvain,Wu, Yong-Jin,Meignan, Gérard
, p. 10332 - 10349 (2007/10/03)
Ketene acetal 25 was converted into silyl enol ether 20, which underwent a Diels-Alder reaction with methyl (E)-3-nitropropenoate to afford ketone 27. This was converted by two routes into (±)calicheamicinone (1). In the first, modification of the nitro, ester, and allyl substituents gave ketone 38, which reacted stereoselectively with cerium trimethylsilylacetylide to place the acetylene unit syn to the nitrogen function (38 → 39). Further elaboration took the route as far as aldehyde 42. A slightly different series of reactions served to convert ketone 27 into tricyclic ketone 43. This also reacted with cerium trimethylsilylacetylide, but in the opposite stereochemical sense to 38, so as to place the acetylene unit anti to the nitrogen function (43 → 50). Further elaboration took this second route as far as lactone 44. Both 42 and 44 serve as advanced intermediates for the synthesis of (±)-calicheamicinone. The monoacetylenic aldehyde 42 reacted stereoselectively with cerium trimethylsilylacetylide to give the bis(acetylene) 53 as the major product. This was elaborated into lactone 60, which was desaturated (60 → 68) and methoxycarbonylated on nitrogen. The acetylenic silyl groups were then removed, so as to generate syn bis(acetylene) 72, and the terminal acetylenic hydrogens were replaced by iodine. The resulting diiodide 81 formed the cyclic enediyne 82 on reaction with (Z)-1,2-bis(trimethylstannyl)ethene in the presence of (Ph3P)4Pd, and the enediyne was converted into (±)calicheamicinone. syn-Bis(acetylene) 72 was also synthesized from the other advanced intermediate (lactone 44), using, as a key step, free radical bromination of the derived unsaturated lactone 77. The resulting bromo lactones 78 were converted into an aldehyde ester 79, and this reacted stereoselectively with cerium trimethylsilylacetylide to give 80, convertible by the action of TBAF into 72.
Synthesis of the antitumor agent aglycon (±)-calicheamicinone using an o-quinone monoketal strategy
Churcher, Ian,Hallett, David,Magnus, Philip
, p. 10350 - 10358 (2007/10/03)
Commercially available 5-methoxysalicylic acid 16 was converted into the o-quinone monoketal 21, which was attached to the enediyne 22, resulting in 23. After protection of the tert-alcohol 24 and conversion of the ester 25 to aldehyde 28, treatment with
Total synthesis of calicheamicin γ1I. 2. Development of an enantioselective route to (-)-calicheamicinone
Smith,Pitsinos,Hwang,Mizuno,Saimoto,Scarlato,Suzuki,Nicolaou
, p. 7612 - 7624 (2007/10/02)
The first enantioselective total synthesis of (-)-calicheamicinone (3), the naturally occurring antipode of the calicheamicin aglycon, has been achieved. The key elements of the synthesis are as follows: (i) the use of an asymmetric allylboration reaction
Total synthesis of calicheamicinone: New arrangements for actuation of the reductive cycloaromatization of aglycon congeners
Haseltine, John N.,Cabal, Maria Paz,Mantlo, Nathan B.,Iwasawa, Nobuharu,Yamashita, Dennis S.,Coleman, Robert S.,Danishefsky, Samuel J.,Schulte, Gayle K.
, p. 3850 - 3866 (2007/10/02)
The total synthesis of dl-calicheamicinone (1) has been accomplished. The key elements of the synthesis were (i) an application of the Becker-Adler reaction to reach compound 91, (ii) an application of the concept of in situ protection to deliver lithiate
