124689-64-1Relevant articles and documents
BIOCATALYTIC SYNTHESIS OF CRYPTOPHYCIN ANTICANCER AGENTS
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Paragraph 0017; 0023; 0156; 0157, (2021/04/02)
The disclosure provides cryptophycin intermediates, cryptophycin analogs, and cryptophycin chimeric molecules useful in treating cancer, as well as methods of producing these compounds and methods of treating cancer.
Total synthesis of cryptophycin 3
Danner, Paulami,Bauer, Matthias,Phukan, Prodeep,Maier, Martin E.
, p. 317 - 325 (2007/10/03)
The depsipeptide cryptophycin 3 (5) and the cryptophycin analogue 43 were prepared from the corresponding four subunits, The tripeptide analogue 34 was acquired from the starting amino ester 33, which contains fragments D and C. After extension at the car
Total Synthesis of Cryptophycins-1, -3, -4, -24 (Arenastatin A), and -29, Cytotoxic Depsipeptides from Cyanobacteria of the Nostocaceae
White, James D.,Hong, Jian,Robarge, Lonnie A.
, p. 6206 - 6216 (2007/10/03)
A convergent synthesis of cryptophycins has been developed in which (5S,6R)-5-hydroxy-6-methyl-8-phenylocta-2(E),7(E)-dienoic acid (A) is coupled with an amino acid segment (B). Two stereo-selective routes to A are described, the first employing allylatio
Total synthesis of cryptophycins and their 16-(3-phenylacryloyl) derivatives
Rej, Rabindra,Nguyen, Dieu,Go, Brian,Fortin, Samuel,Lavallee, Jean-Francois
, p. 6289 - 6295 (2007/10/03)
Cryptophycin A, a cyclic depsipeptide isolated from the blue-green alga (cyanobacterium) Nostoc sp.GSV 224, has shown excellent activity against solid tumors implanted in mice. The benzylic epoxide, which was shown to be very important for biological activity, is also fairly unstable under both acidic and alkaline conditions. The high doses needed to observe in vivo activity might be a result of this instability. In order to solve this problem while preserving the electrophilic character of the benzylic position, enones 1 and 2 have been proposed as promising analogs of the natural product, and a convergent total synthesis of these compounds is described. In addition, the same strategy was used to prepare Cryptophycins A,B, C, and D.
Total synthesis of cryptophycins via a chemoenzymatic approach
Salamonczyk, Grzegorz M.,Han, Kang,Guo, Zhi-Wei,Sih, Charles J.
, p. 6893 - 6900 (2007/10/03)
A highly convergent synthesis of cryptophycins in their enantiomerically-pure forms was achieved. Our strategy consists of the synthesis of the two units 3 and 4 and linking them together to form the macrocyclic ring. The upper unit 3 was prepared from 10 in four steps, and the lower unit 4 was prepared from 20 in three steps. Enantioselective biocatalytic methodology was used to prepare the requisite chiral building blocks, (R)-11 and (R)-19. The stereochemical versatility of this synthetic approach is demonstrated by the synthesis of cryptophycin A and the four diastereomers of cryptophycin C.
Structure determination, conformational analysis, chemical stability studies, and antitumor evaluation of the cryptophycins. Isolation of 18 new analogs from Nostoc sp. strain GSV 224
Golakoti, Trimurtulu,Ogino, Junichi,Heltzel, Carl E.,Le Husebo, Trang,Jensen, Craig M.,Larsen, Linda K.,Patterson, Gregory M. L.,Moore, Richard E.,Mooberry, Susan L.,Corbett, Thomas H.,Valeriote, Frederick A.
, p. 12030 - 12049 (2007/10/03)
Using a modified isolation procedure devoid of methanol, 18 new cyclic cryptophycins have been isolated from Nostoc sp. GSV 224 as minor constituents in addition to cryptophycins-1 (A), -2 (B), -3 (C), and -4 (D). Acyclic cryptophycins are not found, indicating that the previously reported cryptophycins-5 (E methyl ester), -6 (F methyl ester), and -7 (G) are artifacts produced as a consequence of using methanol in the isolation scheme. Seventeen of the new cyclic analogs differ in structure in either one of the two hydroxy acid units, viz. unit A [(5S,6S,7R,8R)-7,8-epoxy-5-hydroxy-6-methyl-8-phenyl-2(E)-octenoic acid for cryptophycin-1 or (5S,6S)-5-hydroxy-6-methyl-8-phenyl-2(E),7(E)-octadienoic acid for cryptophycin-3] and unit D [(2S)-2-hydroxy-4-methylvaleric acid], or one of the two amino acid units, viz. unit B [(2R)-2-amino-3-(3-chloro-4-methoxyphenyl)propionic acid] and unit C [(2R)3-amino-2-methylpropionic acid], found in the cyclic ABCD peptolide. In unit A of cryptophycins-26, -28, -30, and -40, the methyl group on C-6 is missing or the Δ2-double bond is hydrated. In unit B of cryptophycins -16, -17, -23, -31, -43, and -45, the aromatic ring is phenolic and/or possesses two or zero chlorines. In unit C of cryptophycins 21 and -29, the methyl group on C-2 is missing. In unit D of cryptophycins -18, -19, -49, -50, and -54, a different alkyl group (propyl, isopropyl, or sec-butyl) is attached to C-2. Only one of the new analogs, cryptophycin-24, differs in structure for two units by lacking chlorine in unit B and the methyl group in unit C. Revised structures are presented for cryptophycins-5, -6, and -7 and are correlated with cryptophycin-3, the relative stereochemistry of which has been further rigorously established by X-ray crystallography. NOE studies show that the preferred conformations of most cryptophycins in solution differ from the conformation of cryptophycin-3 in the crystal state. Although cryptophycin-1 is relatively stable at pH 7, both in ionic and nonionic media, the ester bond linking units C and D is fairly labile to solvolysis and mild base hydrolysis. Structure-activity relationship studies indicate that the intact macrolide ring, the epoxide group, the chloro and O-methyl groups in unit B, and the methyl group in unit C are needed for the in vivo activity of cryptophycin-1.
Total synthesis of cryptophycins. Revision of the structures of cryptophycins A and C
Barrow, Russell A.,Hemscheidt, Thomas,Liang, Jian,Paik, Seunguk,Moore, Richard E.,Tius, Marcus A.
, p. 2479 - 2490 (2007/10/02)
The convergent total synthesis of cryptophycins C and D is described. It has been shown that in both natural products the absolute configuration of the α-amino acid corresponds to the D-series. The structural assignment for cryptophycin C has been correct
