Patterned synthesis

Review Problem 17 Design a synthesis for TM 206, an intermediate in Crandall and Lewton s biogenetically patterned synthesis of cedrene ( J. Amer. Chem. Soc.. 1969, 91, 2127). 

Cruz-Ortega, R., Ayala-Cordero, G. and Anaya, A.L. (2002). Allelochemical stress produced by Callicarpa acuminata effects on catalase activity and protein pattern synthesis of crop plants. Physiologia Plantarum 116 20-27... 

Konig WA, Icheln D, RungeT, Pforr I, Krebs A, Cyclodextrins as chiral stationary phases in capillary gas chromatography, VII, Cyclodextrins with an inverse substitution pattern — Synthesis and enantioselectivity, /Resolut Chromatogr 13 702-707, 1990. 

Table 13.5.1. Technological conqrounds from nature, semisynthesis, or patterned synthesis...

Patterned synthesis is also an active line (Table 15. III), best illustrated by ephedrine, which served as a model for many synthetic CNS-active drugs (Table 15.III). Patterned synthesis is aimed at... 

Peptidomimetics is an active branch of patterned synthesis. A notable family of tumor-avid peptides was derived from synthesis patterned on neurotensin, a peptide constituted of 13-amino acids. These synthetic peptides bind to the NT receptors expressed by many forms of cancer, which may serve to map the tumor, delivering radionuclides in situ (Waibel 2000). Molecules that, like the peptides, are constituted of repetitive blocks, are much simpler to synthesize than those composed of non-repetitive units. Given the powerful bioactivity, and improved stability on systemic administration, synthetic peptides may become rewarding it as it has been estimated, one in two men, and one in three women, will get cancer in their lifetime. 

At the borderline between semisynthesis and patterned synthesis, versatile total syntheses may provide access to diversified bioactive structures. Classically, analogues of the active drug are sought that avoid the resistance developed by pathogens and show reduced side effects. In lucky cases, chemical simplification has afforded the wonder drug. This is the case of sodium valproate (2-propylvaleric acid sodium salt), which was synthesized in the fall of the XIX century and nearly a hundred years later became a leading drug in the treatment of epilepsy. 

Since the successful biogenetically patterned synthesis of the galanthamine skeleton from O V-dimethylnorbelladine (397) by oxidative coupling performed by Barton and Kirby several attempts have been carried out along these lines. However, several norbelladine derivatives were used in the hope that a decrease in the nitrogen lone pair availability might increase the yields in the oxidation phase. 

In a biogenetically patterned synthesis, the cyclization of epoxygeranylgeraniol with boron trifluoride etherate has been shown to afford the compounds (103) and the pimaradienols (104). The cyclization of epoxygeranylgeranyl pyrophosphate by kaurene synthetase affords the epimeric 3-hydroxykaurenes. A cyclization of olefinic jS-keto-esters (105) to the bicyclic compound (106) has formedthe basis of a novel synthesis of A -podocarpen-13-one (107), a compound which is an intermediate in several diterpenoid total syntheses. Synthetic approaches to the... 

A biogenetically patterned synthesis of the morphine alkaloids Mami, Ismail Sadeg... 

Cherylline.—An interesting biogenetically patterned synthesis of (i)-cherylline (232) has been carried out (Scheme 15). °... 

Haslam, E. Biogenetically Patterned Synthesis of Procyanidins. J. Chem. Soc., Chem. Commun., 594 (1974). 

Giese, H., Klein, E., Burmester, S. Pattern Synthesis from Multiple Scenarios for Parameterized Real-Timed UML Models. In Leue, S., Systa, T.J. (eds.) Scenarios Models, Transformations and Tools. LNCS, vol. 3466, pp. 193-211. Springer, Heidelberg (2005)... 

This biosynthetic proposal became an indirect evidence by Brown et al. who demonstrated a biogenetically patterned synthesis of CPT and 20-deoxycamptothecin starting from strictosidine/vincoside. The complete route from 44 to racemic CPT has been completed by chemical transformation involving all of the postulated intermediates in the biosynthesis scheme [170]. Other biomimetic synthesis of CPT has also been reported [171]. 

Hashimoto T, Matsuda J, Yamada Y (1993) Two-step epoxidation of hyoscyamine to scopolamine is catalyzed by bifunctional hyoscyamine 6 3-hydroxylase. FEBS Lett 329 35-39 Hayslett RL, Tizabi Y (2003) Effects of donezipil on DOI-induced head twitch response in mice impUcations for Tourette s syndrome. Pharmacol Biochem Behav 76 409-415 Hayslett RL, Tizabi Y (2005) Effects of donezipil, nicotine and haloperidol on the central serotoneigic system in mice impUcations for Tourette s syndrome. Pharmacol Biochem Behav 81 879-886 Hedges SH, Herbert RB (1979) An economical, biogenetically patterned synthesis of the alkaloid ipalbidine. J Chem Res Synopses 1... 

Merlini, L., and A. Zanarotti A Biogenetically Patterned Synthesis of ( )-Eusi-derin. Tetrahedron Letters 1975, 3621. 

Haslam E 1974 Biogenetically patterned synthesis of procyanidins. J Chem Soc Chem Commun 594-595... 

Butenandt has similarly shown that the ommochrome eye pigments found in Drosophila species were not formed in some mutants imless kynurenine (24) or 3-hydroxykynurenine (88) was provided in the diet. In addition xanthommatin (84), rhodommatin and ommatin C, ommochromes synthesised by the blowfly Callio-phora erythrocephala, were demonstrated to possess radioactivity after injection of either d L-3-[ C]-tryptophan or D l-5-[ C]-kynurenine . Based on these observations Butenandt proposed that xanthommatin (84) was biosynthesised by an oxidative condensation of two molecules of 3-hydroxykynurenine (88) and a biogenetically patterned synthesis of (84) was achieved by treatment of 3-hydroxykynurenine (88) with potassium ferri-cyanide. The synthesis proceeds probably by oxidation to the... 

Following up this idea they synthesized )8-carboline and 1-methyl-/3-carboline by reaction of tryptophan with formaldehyde and acetaldehyde, respectively, under oxidizing conditions. The steps of this biogeneticaUy patterned synthesis have been repeatedly studied and are fuUy discussed in Sections III, A, l,aand III,E,2,a,i. The formation of l,2,3,4-tetrahydro-)8-carbolines as the initial step in the biogenesis of jS-carboline alkaloids, by reaction of tryptophan or trypta-mine or the corresponding hydroxylated derivatives with aldehydes or a-keto acids, derivable from a-amino acids, is a widely held concept. Two lines of circumstantial evidence favor this hypothesis. First, a number of simple l,2,3,4-tetrahydro-)8-carboline derivatives have been found to occur naturaUy. l-Methyl-l,2,3,4-tetrahydro-]8-carbo-line (461 = B = H eleagnine) has been isolated from Elaeagnus... 

Lactonization of a hydroxy-acid to a butyrolactone is achieved, using dimethyl-formamide dineopentyl acetal, during a synthesis of oxygenated nor-heliango-lides. The chiral lactone (164) is prepared from (iJ)-malic acid, its dianion is alkylated at carbon to give the /ra/i5-disubstituted lactone (165) in moderate yield, and this is used in a synthesis of (—)-aplysistatin (Scheme 94). An independent, biogenetically patterned synthesis of this natural product, using tetronic acid intermediates, has been described. ... 

Robins has outlined an interesting biogenetically patterned synthesis of the pyrrolizidine alkaloid trachelanthamidine (107). The alkaloid, together with its epimer isoretronecanol (112) (- 5%), was produced ( 40%) when homospermidine (106) was incubated with diamine oxidase and catalase at 27 °C in phosphate buffer at pH 7.5 for six days. 

A biogenetically patterned synthesis of the indolizine alkaloid septicine has been reported. The uncommon addition of a jS-keto acid to an imine was the important step which created the bicyclic structure shown in Scheme 119. A neat intramole-... 

The tricyclic hydrocarbon hirsutene (94), isolated recently from Coriolus consors, is a probable precursor for coriolin (95), found in C. consors, and also for hirsutic acid (96), isolated from Stereum hirsutum. In a biogenetically patterned synthesis of hirsutene, Ohfume et al. have shown that treatment of the tricyclic hydrocarbon (92) with a catalytic amount of toluene-p-sulphonic acid leads to the endo-isomer (93), in 95% yield, which by manipulation of the double bond can be... 

Schwartz MA, Mami IS (1975) A biogenetically patterned synthesis of the morphine alkaloids. J Am Chem Soc 97 1239-1240... 

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