Cryptophycins structure

Stereospecific deoxygenations in the cryptophycin family of natural products from Nostocaceae were reported by Moore [47]. The products were important in the elucidation of the natural product s structure and for the preparation of novel cryptophycin derivatives. 

Li T, Shih C (2002) Structure Activity Relationships of Cryptophycins, A Novel Class of Antitumor Antimitotic Agents. Front Biotechnol Pharmaceut 3 1972... 

Barrow RA, Hemscheidt T, Liang J, Paik S, Moore RE, Tius MA (1995) Total Synthesis of Cryptophycins. Revision of the Structures of Cryptophycins A and C. J Am Chem Soc 117 2479... 

Golakoti T, Ogino J, Heltzel CE, Husebo TL, Jensen CM, Larsen LK, Patterson GML, Moore RE, Mooberry SL, Corbett TH, Valeriote FA (1995) Structure Determination, Conformational Analysis, Chemical Stability Studies, and Antitumor Evaluation of the Cryptophycins. Isolation of 18 New Analogs from Nostoc sp. Strain GSV 224. J Am Chem Soc 117 12030... 

Chaganty S, Golakoti T, Heltzel C, Moore RE, Yoshida WY (2004) Isolation and Structure Determination of Cryptophycins 38, 326, and 327 from the Terrestrial Cyanobacterium Nostoc sp. GSV 224. J Nat Prod 67 1403... 

The cryptophycins (e.g. 16) form a group of depsipeptide antibiotics with a (R)-/7-AiB (R)-2 or / -Ala 1 substructure. They have already been isolated from cyanobacteria (Nostoc sp., see below) [47] arenastatin A 17 has been isolated from a marine sponge [42]. The cryptophycins are new lead structures within cancer drug research for their potent tumor-selective cytotoxicity [92]. The synthetic analog cryptophycin-52 (= 6-methylcryptophycin-l, LY-355703, 18) has reached clinical phase II trials [93]. 

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 essential for the in vivo activity of cryptophycin 1 (Fig. 51) ... 

Figure 9 Chemoenzymatic synthesis of cryptophycin analogues using the excised Crp TE domain. Recombinant TE from this prototypical PKS/NRPS system tolerates structural modifications on its native seco-cryptophycin substrates. Two different tags are used to mimic the T domain to which the PK/NRP intermediate is tethered in vivo.

Arenastatin A, cryptophycin-24, a 16-membered cyclodepsipeptide dep-sipeptides) isolated from the Okinawan marine sponge Dysidea arenaria with structural similarity to cryptophycins and identical with cryptophycin-24. Arenastatin A inhibits microtubule assembly in vitro. It binds to tubulin at the rhizoxin/maytansine binding site. The total synthesis was described in 2000 [M. Kobayashi et al., Chem. Pharm. Bull. 1994, 42, 2196 M. J. Eggen etal., Org. Chem. 2000, 65, 7792]. 

Cyanobacteria are also sources of substances of pharmaceutical interest, for example, antibiotics [54]. Moore et al. isolated structurally unique cytotoxins from a lipophilic extract of Nostoc spp. GV 224. These cyclic depsipeptides called cryptophycins showed both solid tumor and tumor-selective cytotoxicity in the Corbett assay and in vivo studies revealed them to be very active against a number of tumors implanted in mice [55]. These studies may lead to the discoveries of new antitumor drags [56]. 

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