A-Seco derivatives

The above syntheses were preceded by model investigations (143), as a result of which several unnatural 1,2-secoisoquinolines, e.g., 175-177 were synthesized (Scheme 30). Finally, a reaction reported by Bentley and Murray (144) is worth mentioning since it may serve as a model for biosynthetic conversion of benzylisoquinoline alkaloids to the seco analogs (Scheme 30). Heating of ketolaudanosine (174) with methyliodide unexpectedly formed a seco derivative 175 along with to the quaternary salt. By all probability it arose from the methiodide of 174 by air oxidation followed by ring opening. 

New tirucallane triterpenoids are adenophorate (70) (T-ray analysis) from Adenophora triphylla (Campanulaceae),32 and the ring a seco derivatives (71) and (72) from Guarea cedrata (Meliaceae).52 Treatment of the 7a-hydroxy- or 7-keto-apotirucall-14-enes (73)—(75) with monoperphthalic acid affords the corresponding 14a,15a-epoxides.53... 

Treatment of the enone (69) with an excess of the diene (70) in the presence of aluminium trichloride and 4,4-thiobis-(6-t-butyl-3-methylphenol) gave the tricyclic ketone (71) (40%) as the sole Diels-Alder product. Reduction then afforded the lactone (72) whose constitution and stereochemistry were established by X-ray analysis. Finally, demethylation gave the racemic alcohol (73) which differs from the quassin skeleton only in the stereochemistry at C-9. The Diels-Alder reaction also plays a key role in two other de novo syntheses. The ring A seco-derivative (75) has been prepared from the adduct (74), and the ring A nor-compound (77), a possible intermediate for the synthesis of quassimarin (78), has been obtained from the Diels-Alder product (76). ... 

A series of A-seco derivatives was prepared by Ojima and Appendino from the C-14/3-hydroxy derivative 2.3.1 (50, 57). Cleavage of the 1,2-diol of 2.3.1 with periodate gave the ketoaldehyde 2.3.9 as its hemiacetal, and this could be reduced to the diol 2.3.10 or converted to the amino alcohol 2.3.11. Acylation with /3-lactam and deprotection gave the analogs 2.3.12-2.3.15, depending on which /3-lactam was used and on whether the amino alcohol or the diol was esterified. Analogs 2.3.12 and 2.3.13 were only 15-20 times less cytotoxic than taxol, but analogs 2.3.14 and 2.3.15 were over 100 times less cytotoxic than taxol. 

The synthesis of the CG525155 (a neutral endopeptidase inhibitor) required a Pd catalyzed Tsuji-Trost reaction as the key step following the strategy described by Johnson. Starting from the optically active allenyl amino acid methylester 91 (synthesized in several steps from 90), the seco-derivative 92 as the crucial precursor was generated in several steps in high yield. The Pd (0)... 

A simple method was developed for the cleavage of the C-2—C-3 bond of indole alkaloids by the use of formic acid-formamide as reagent. Thus 2,3-seco derivatives of yohimbine (74), hirsutine (58), and reserpine (109) were prepared... 

The first arene oxides to be synthesized (1964) were obtained by the cyclization of appropriate seco derivatives. 0,0-Diformylbiphenyl derivatives, when treated with Mark s reagent [tris(dimethylamino)phosphine], gave arene oxides [Eq. (3)]. Thus K-region epoxides from phenanthrene and its analogs, benz[a]anthracene and its 7,12-dimethyl analog, have been prepared.34... 

RB Woodward, E Logusch, KP Nambiar, K Sakan, D Ward, B-W Au-Yeung, P Balaram, LJ Browne, PJ Card, CH Chen, RB Chenevert, A Fliri, K Frobel, H-J Gais, DG Garrat, K Hayakawa, W Heggie, DP Hesson, D Hoppe, 11 loppe et al. Asymmetric total synthesis of erythromycin. 1. Synthesis of erythronolide A seco acid derivative via asymmetric induction. J Am Chem Soc 103 3210-3213, 1981. 

The asymmetric syntheses of tetrahydroisoquinoline derivatives were also reported. Optically pure 3,4-disubstituted tetrahydroisoquinolines such as 78 were prepared by Friedel-Crafts cyclization of amino alcohols 77 <02TL1885>. Enantioselective syntheses of dihydropyrrolo[2,l-a]isoquinolines via a highly diastereoselective, chiral auxiliary assisted N-acyliminium cyclization was disclosed <02SL593>. The enantioselective synthesis (-)-tejedine, a seco-bisbenzyltetrahydroisoquinoline was also reported. One key step in this synthesis involved a chiral auxiliary-assisted diastereoselective Bischler-Napieralski cyclization <02OL2675>. Additionally, an asymmetric Bischler-Napieralski was reported for the preparation of 1,3,4-trisubstituted 1,2,3,4-tetrahydroisoquinolines <02JCS(P1)116>. 

Except for the C-13 substitutions, the most extensively studied in A ring modifications are contracted ring (A-nor), opened ring (A-seco), and the 11,12-dihydro analogs. Although some derivatives showed comparable activities, most of them were less active than paclitaxel. 

A-Homocholestane derivatives have been obtained by the Demjanov ring-enlargement reaction. Transannular solvolysis reactions have been observed in seco-steroids of type (393) containing a ten-membered ring. Thus, treatment of (393) in aqueous acetone solution produced 5(10—> l H)abeo-5fi-cholest-10(19)-ene 3/8-acetate (394) in high yield. ... 

Although the precise mechanism of the coupling reaction is not thoroughly established, one can visualize the formation of (71) as arising from initial fragmentation of the C(16)—C(21) bond of (69), followed by condensation of vindoline with the more accessible a face of the iminium ion (73). The impact of the Polonovski approach in this area is emphasized by the fact that all other attempts to couple vindoline with 16,21-seco derivatives of catharanthine lead invariably to formation of the unnatural dimer. A Polonovski reaction was also a key step in the subsequent elaboration of anhydrovinblastine (71) to (68). ... 

Curtins reaction conditions converted the A-seco-keto-acid (442) into A-nor-3-azacholest-3(5)-ene (443), which was reduced (HCl-NaBH4) to the pyrrolidine analogue (444). The keto-acid (442) reacts with hydrazine or substituted hydrazines to give 4-amino-4-aza-steroids (445)—(449). The phenylhydrazine derivatives (446) could be cyclized to the indole (450). " ... 

---