193146-63-3

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Chemical Properties

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Upstream product

• 193146-53-1 (5S,8R,9S,10S,17S,Z)-9-(tert-butyldimethylsilyloxy)-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,10,14,19,19,20,20-tridecamethyl-17-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-4,18-dioxa-3,19-disilahenicos-14-en-7-one 
• 477290-40-7 (12Z,16E)-(3S,6R,7S,8S,15S)-3,7,15-tris-(tert-butyl-dimethyl-silanyloxy)-1-((S)-10,10-dimethyl-3,3-dioxo-3-thia-4-aza-tricyclo[5.2.1.0]dec-4-yl)-4,4,6,8,12,16-hexamethyl-17-(2-methyl-thiazol-4-yl)-heptadeca-12,16-diene-1,5-dione 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 355009-02-8 (S)-4-Benzyl-3-((S)-6-iodo-2-methyl-hept-6-enoyl)-oxazolidin-2-one 
• 39238-07-8 4-(chloromethyl)-2-methyl-1,3-thiazole 
• 121587-29-9 (3S)-3-methyl-1-phenylsulfonylbutan-4-ol 
• 188899-14-1 (3S,4E)-3-(tert-butyldimethylsilyloxy)-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)pent-4-en-1-ol 
• 89922-82-7 3-(tert-butyldimethylsilanyloxy)propionaldehyde 
• 20949-84-2 2-methylthiazole-4-carbaldehyde 
• 1353777-77-1 (3S,5Z)-2-(bromomethyl)-6,10-dimethylundeca-1,5,10-trien-3-yl pivaloate 
• 1353777-78-2 (3S,5Z)-6,10-dimethyl-2-[(2-methylthiazol-4-yl)methyl]undeca-1,5,10-trien-3-yl pivaloate 
• 1353777-79-3 (3S,1E,5Z)-2,6,10-trimethyl-1-(2-methylthiazol-4-yl)undeca-1,5,10-trien-3-ol 
• 412926-87-5 4-[(3S,1E,5Z)-3-(tert-butyldimethylsiloxy)-2,6,10-trimethylundeca-1,5,10-trienyl]-2-methylthiazole 
• 188899-12-9 (-)-(3S)-3,5-bis(tert-butyldimethylsilyloxy)-pentan-2-one 

Downstream Products

• 193146-26-8 (3S,6R,7S,8S,12Z,15S,16E)-3,7-bis{[tert-butyl(dimethyl)silyl]oxy}-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxoheptadeca-12,16-dienoic acid 
• 152044-54-7 epothilone B 
• 189453-35-8 (4S,7R,8S,9S,13Z,16S,1'E)-4,8-di-tert-butyldimethylsilyloxy-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-1,3-thiazol-4-yl)-1-ethenyl]-1-oxa-13-cyclohexadecene-2,6-dione 
• 189453-10-9 epothilone D 
• 219989-84-1 ixabepilone 

Relevant academic research and scientific papers

PROCESS FOR THE PREPARATION OF (1S,3S,7S,10R,11S,12S,16R)-7,11-DIHYDROXY-8,8,10,12,16-PENTAMETHYL-3-[(1E)-1-METHYL-2-(2-METHYL-4-THIAZOLYL)ETHENYL]-17-OXA-4-AZABICYCLO[14.1.0]HEPTADECANE-5,9-DIONE AND INTERMEDIATES THEREOF

The present invention relates to an improved process for the preparation of (1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[(1E)-1-methyl-2-(2- methyl-4-thiazolyl)ethenyl]- 17-oxa-4-azabicyclo[ 14.1.0]heptadecane-5,9-dione represented by the following structural formula I and intermediates thereof. The present invention also provides novel intermediate compounds useful for the preparation of compound of formula I and its intermediates.

Synthesis of epothilone D with the forced application of oxycyclopropane intermediates

The total synthesis of epothilone D with six-fold application in the intermediate stages of successive cyclopropanation - opening or cleavage of the three-membered ring was performed. These transformations underlie the new stereoselective method developed for coupling fragments C7-C 12 and C13-C21 in the target molecule.

Total synthesis of epothilone D by sixfold ring cleavage of cyclopropanol intermediates

The ring-opening or ring fragmentation reactions of cyclopropanol intermediates are used in the total synthesis of epothilone D for the creation of trisubstituted double bonds, an ethyl ketone functionality, as well as for the protection of carboxylic and ester groups. Epothilone D is obtained in 1.6% overall yield (24 steps in the longest linear sequence) starting from (R)-methyl 2,3-O-isopropylideneglycerate. The key cyclopropanol intermediates are efficiently obtained by titanium(IV)-catalyzed reactions of readily available esters with Grignard reagents. Crown Copyright

Diastereoselective Titanium Enolate Aldol Reaction for the Total Synthesis of Epothilones

(Matrix Presented) The development of a highly diastereoselective addition of the titanium enolate derived from ketone 1 to aldehyde 2 offers an efficient entry to the total synthesis of the epothilone family. The new aldol process is robust and tolerates

Total synthesis of epothilones B and D

(Matrix presented) A highly convergent total synthesis of the natural products epothilone B and D is described. The route is highlighted by efficient generation of a C12-C13 trisubstituted olefin which exploits a sequential Nozaki-Hiyama-Kishi coupling and a stereoselective thionyl chloride rearrangement.

Total Syntheses of Epothilones B and D

Total syntheses of the microtubule stabilizing antitumor drugs epothilone B and D are described, starting from optically pure (S)-malic acid and methyl (R)-3-hydroxy-2-methylpropionate. The synthesis is highly convergent by coupling the three fragments C1-C6 (fragment D), C7-C10 (fragment C), and C11-C21 (fragment B). Key steps are two stereoselective Wittig type olefinations to generate the 12,13- and 16,17-double bonds, an enantioselective Mukaiyama aldol addition to synthesize fragment D, and a sulfone anion allyl iodide alkylation to connect fragments B and C. Finally fragment D was attached to the B + C fragment via aldol addition.

Easy access to the epothilone family - Synthesis of epothilone B

An easy access to four out of five naturally occurring epothilones (A- E, 1-5) is reported. Key steps are an enantioselective Mukaiyama type aldol reaction, (E)- and (Z)-selective olefinations, and a sulfone alkylation.

Total syntheses of epothilones A and B via a macrolactonization-based strategy

The total syntheses of epothilones A (1) and B (2) and several analogues thereof are described. The reported strategy relies on a macrolactonization approach and features selective epoxidation of the macrocycle double bond in precursors 3 and 4 (Scheme 1), respectively, as well as high convergency and flexibility. Building blocks 9-12 and 15 were constructed by asymmetric processes and coupled via Wittig, aldol, and macrolactonization reactions to afford the basic skeleton of epothilones and that of several of their analogues by a relatively short route. The utilization ofintermediate 14, obtained via a stereoselective Wittig reaction and its Enders coupling to SAMP hydrazone 13 (Scheme 8), in combination with a stereoselective aldol reaction with the modified substrate 69 (Scheme 10) improved the stereoselectivity and efficiency of the total synthesis of these new and highly potent microtubule binding antitumor agents.