Experimental and theoretical approaches into the C- and D-ring problems of sterol biosynthesis. Hydride shift versus C-C bond migration due to cation conformational changes controlled by the counteranion

The C- and D-ring problems of sterol biosynthesis, how an enzyme overcomes the Markovnikov wall, were investigated by using a model compound from an experimental as well as theoretical standpoint. When model diol 20 was treated with BF₃·Et₂O, SnCl₄, TiF₄, Sc(OTf)₃, FeCl₃, or TfOH, spirocyclic ether 21 was formed as the sole product via a tert-cationic intermediate 16 through 1,2-hydride shift. However, the treatment with TiCl₄ afforded six-membered ring products 22, 23, 24, 25, 26, and 27 via the ring expansion into the unstable six-membered ring secondary cation 17. Occurrence of both α and β chloride 23 and 24 is distinctive evidence of the existence of secondary cation 17, ruling out the idea of the concerted mechanism. Molecular mechanics calculations of the naked cation 15 elucidated two possible conformers, parallel 15-I (five membered ring and cationic plane) that is favorable for the hydride shift generating 16 and perpendicular 15-II leading to C-C bond migration to 17. The first ab initio calculation of the cation conformation in the presence of counteranions such as [TiCl₄OH]⁻, [TiF₄OH]⁻, [BF₃OH]⁻, and [OTf]⁻ entirely supported our experimental results. Although the counteranion [TiCl₄OH]⁻ stabilizes perpendicular cation 15-II, it destabilizes the parallel conformer 15-I significantly, and thus, the C-C bond migration to 17 becomes the only possible pass. On the other hand, [TiF₄OH]⁻, [BF₃OH]⁻, and [OTf]⁻ stabilize parallel conformer 15-I and the hydride shift to 16 becomes the only possible pass. The relative location or distance of the counteranion from the cation should be the biggest factor to control the stability and, thus, the conformation of the cation. Our results indicate that the carboxylate anions in the enzyme cavity enable to control the conformation of pre-C-ring cationic intermediate 3 to be perpendicular leading to six-membered C-ring secondary cation 4. The parallel conformation of the cation 5 could lead to hydride shift to give tirucallanoids or lanostanoids. Therefore, this result is the first example that overcame the big Markovnikov wall experimentally and theoretically at least to our knowledge.     

To seek an approach toward the chemical conversion of C19-diterpenoid alkaloids to taxoids

This study, as a part of conversion of the C₁₉-diterpenoid alkaloids to the taxoids, described the search of a suitable route to the key intermediate B with four approaches (ABC, ACB, BCA, and CAB) designed and examined. In these cases, a new and efficient approach (CAB) toward the synthesis of the vital intermediates 51 or 52 has been developed. The key steps include the use of a semipinacol rearrangement treatment of 41 with NaOH/DMF under refluxing conditions for 30 min to afford 42, and the rupture of the N-C-19 bond found in 45 or 48 to give 51 or 52, respectively, through NBS imination followed by the creation of the oxaziridine 47 or the nitrone 50 and finally HIO₄ oxidation cleavages.     

Enantioselective total synthesis of cineromycin B

The enantioselective total synthesis of cineromycin B, a 14-membered unsaturated macrolide with two doubly allylic alcohols, was completed using a Julia coupling, an oxidative [2,3]-sigmatropic rearrangement of selenide, and a Yamaguchi macrolactonization as key reactions.     

[Co(3,3-tri)(amp)Cl]~(2+)四个经式异构体取代、重排反应及其与结构关系的研究

对犤Co(3,3-tri)(amp)Cl犦2+四个几何经式异构体在不同条件下的取代及重排反应进行考察的实验结果表明,四个几何经式异构体碱性环境下的水解速率没有显著的差异,cis异构体比trans异构体约快20倍。实验中没有观察到面式异构体。在100℃二甲亚砜中加热的重排反应实验中可观察到异构体进行配体翻转的历程,如异构体m1-Cl转化为m4-Cl,m2-Cl转化为m3-Cl。m3和m4相对较稳定。利用量子化学从头计算法,在赝势基组RHF/LANL2DZ的水平上对该体系各异构体进行了基态能量、几何优化的计算,与已测定的异构体m3犤ZnCl4犦H2O和m4犤ZnCl4犦晶体结构参数比较,键长及键角的相对误差不超过3%。根据各异构体基态能量说明了各异构体的平衡分布;讨论了键角变形性大小与各异构体反应性大小的关系。     

New oxidative transformations of alkenes and alkynes under the action of diacetoxyiodobenzene

Treatment of alkenes and alkynes with diacetoxyiodobenzene activated by mineral and organic acids predominantly results in oxidative rearrangement. 1,4-Diphenylbutadiene in MeOH gives 3,4-dimethoxy-1,4-diphenylbut-1-ene.Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1669–1675, August, 2004.     

Synthesis and properties ofN-methylmorpholinium 6-amino-3,5-dicyano-1,4-dihydropyridine-4-spirocyclopentane-2-thiolate

The reaction of cyclopentylidenecyanothiocetamide with cyanothioacetamide andN-methylmorpholine gaveN-methylmorpholinium 6-amino-3,5-dicyano-1,4-dihydropyridine-4-spirocyclopentane-2-thiolate, which was used in the syntheses of substituted 2-alkylthiodihydropyridines and pyrazolodihydropyridine. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1849–1851, October. 1997.     

Regioselective boron trichloride-mediated aromatic Claisen rearrangement of resorcinol allyl ethers

The regioselective Claisen rearrangement of resorcinol allyl ethers with boron trichloride was achieved with good selectivity (ca. 13:1) to afford the 6-isomer as major product.     

Wavelength sensitivity of the photoinduced reaction in polycarbonate

Bisphenol A polycarbonate (PC) was irradiated with monochromatic light of wavelengths 260, 280, 300, 320, 340, 400, and 500 nm by use of the Okazaki large spectrograph (OLS). The quantum yield of main-chain scission (?_cs), efficiency of photo-Fries rearrangement (E_r), and effects of wavelength on ?_cs and E_r were investigated. It was found that photodegradation and photo-Fries rearrangement of PC took place by the irradiation of 260–300 nm light, but did not by the irradiation at λ ≧ 320 nm. The ?_cs has a maximum value in the case of the irradiation with 260 nm light, while E_r was found to have a maximum value by the irradiation of 280 nm light. © 1993 John Wiley & Sons, Inc.     

Synthesis and properties of novel diisocyanate based optically active polyimides

A new optically active diisocyanate was prepared from the reaction of l-leucine and pyromellitic dianhydride (PMDA) and subsequent transformation of intermediate imide-containing diacid to diisocyanate via Weinstock modification of Curtius rearrangement. Solution polycondensation reaction of the prepared diisocyanate with PMDA, 3,3,4,4-benzophenonetetracarboxylic dianhydride, and hexafluoroisopropylidene 2,2-bis(phthalic anhydride) resulted in the preparation of novel optically active polyimides. The optimal conditions for polyimidations (reaction duration and temperature programming) were obtained via study of the model compound. The monomer, model compound and polymers were characterized by FTIR, ¹HNMR, mass spectroscopy and elemental analysis and their optical and physical properties were studied as well.     

Chemical Modification of Plant Alkaloids. 4. Reaction of Cotarnine with Bifunctional NH- and CH-Acids

1-Substituted 1,2,3,4-tetrahydroisoquinoline systems were prepared by reaction of cotarnine with the NH-and CH-acids methyl- and acyl derivatives of pyrazole and 1,3-dicarbonyl reagents. Depending on the structure and reaction conditions, bifunctional pyrazole nucleophiles can give substitution products at the N atom, methyl, or acyl group; 1,3-diketones, at the terminal methyl. Rearrangements occurring during the reaction of cotarnine with bifunctional substrates were studied. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 360–364, July–August, 2005.