Antitumor agent

A combination of Cp nCX —A CXC) (where = cyclopentadienyl) effectively promotes the Friedel-Crafts coupling of glycosyl fluorides with aromatic compounds, such as trimethoxyben2ene or methoxynaphthalenes. The derived C-aryl glycosides are potent antitumor agents (39). 

Many notable examples of the synthesis of complex natural products from optically pure starting materials have been reported (70). One synthesis of considerable interest is that of taxol [33069-62-4] (74), a potent antitumor agent used clinically. The starting material (73) used ia the first total synthesis of taxol is produced ia enantiomericaHy pure form from inexpensive and readily available /-camphor [464-48-2] (72) (73). 

Alkan olamines are used in the manufacture of a variety of pharmaceutical compounds. Some of these products include antitumor agents, anti-inflammatory and allergy agents, and anticonvulsants. The Hterature reports ethan olamine derivatives in the treatment of Alzheimer s disease (216), the treatment of cerebral psychoorganic syndromes (217), and veterinary dmgs (218). 

In seeking a synthetic route to an antibiotic antitumor agent, the Thiele-Winter synthon, with 2,3-bis(methoxycarbonyl)-l,4-ben2oquinone [77220-15-6] (60), was used to introduce a required third oxygen linkage (57). A 67% yield of (61) was obtained. 

Sucralfate [54182-58-0] an aluminum salt of sucrose octasulfate, is used as an antacid and antiulcer medication (59). Bis- and tris-platinum complexes of sucrose show promise as antitumor agents (60). Sucrose monoesters are used in some pharmaceutical preparations (21). A sucrose polyester is under evaluation as a contrast agent for magnetic resonance imaging (mri) (61). Oral adrninistration of this substance opacifies the gastrointestinal tract and eliminates the need for purging prior to mri. 

Bleomycin and cyclosporine are the two economically most important streptomycete peptide antibiotics used as antitumor agents and immunomodulators, although dactinomycin is important medically for several tumors (see Chemotherapeutics, anticancer Immunotherapeutic agents). 

Dactinomycin is useful against several tumors especially Wilms tumor of the kidney and rhabdomyosarcoma. Wilms tumor normally requires a combination of surgery, x-ray irradiation, and dactinomycin plus vincristine [57-22-7] or other antitumor agents. Resistance of the multidmg... 

Echinomycin (131) has been shown to be an antitumor agent and to have antiviral and antibacterial properties. Its structure elucidation represents a triumph for and mass spectral studies (75JA2497). It has been demonstrated that echinomycin functions by inhibiting RNA synthesis in organisms such as Staphylococcus aureus. Echinomycin, levomycin and actinoleutin are members of the quinoxaline-peptide antibiotic family and all contain one or more quinoxaline rings (67MI21402). 

Pharmacologically useful isoxazoles (B-82MI41600) include antibacterial sulfonamides (614), (615) and (616), semisynthetic penicillins (617), (618), (619) and (620), semisynthetic cephalosporin (621), anabolic steroid (622), the monoamine oxidase inhibitor (623) (used in psychotherapy), antiinflammatory agent (624) and antitumor agent (625). 

The synthesis of (+)-N-methylmaysenine, a preliminary for the later synthesis of the antitumor agent maytansine, was accomplished by the joining of fragments A and B, chain extension and macrolactam closure using a mixed carboxylic-sulfonic acid anhydride. 

The first synthesis of the potent antitumor agent maytansine was carried out by the elaboration of aldehyde D, an intermediate in the enantioselective synthesis of (-)-A/-methylmaysenine (Ref. 1,2), using enantioselective and diastereoselective steps. 

Bicyclic Core of the Esperamiein/Caliehemicin Class of Antitumor Agents Schreiber, Danishefsky, Magnus,... 

Bleomycin A2 (an antitumor agent u.sed clinically again.st. specific tumors)... 

Nicolaou and co-workers established the severely strained A-ring oxazole (21) in their total synthesis of antitumor agent diazonamide A through initial oxidation of the hindered alcohol of intermediate 20 with TPAP and subsequent Robinson-Gabriel cyclodehydration of the resultant ketoamide with a mixture of POCI3 and pyridine (1 2) at 70°C. ... 

Compounds of B12 series combined with ascorbic acid as potential antitumor agents 98MI56. 

Design of DNA minor-groove binders as new antitumor agents 99F15. 

Development of large-scale synthesis of antitumor agent E09, an indoloquinone derivative 99YGK401. 

Heterocyclic templates and nonpolyglutamatable inhibitors of thymidylate synthase as potential antitumor agents 99JHC827. 

This methodology has been used for the synthesis of the C3-C14 segment 24 of the antitumor agent laulimalide 23 (Scheme 4.22) [35]. The constrained chiral BOX ligand 21c in combination with Cu(OTf)2 afforded dihydropyrane 6f by a cycloaddition reaction in good yield and ee this was converted to the C3-C14 segment 24 via a Ferrier-type rearrangement in several steps. 

Myers has discovered a related reaction of the natural product neocarzinostatine 8 (simplified structure). As in the case of the Bergman cyclization a diradical intermediate is generated by a chemical activation step taking place at the reaction site, where it then can cleave DNA. Because of this feature, together with its discriminating affinity towards different DNA strands, neocarzinostatine is regarded as a potential antitumor agent. 

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