含手性磷酸酯基的寡核苷酸类似物的立体控制性合成

本文总结了近十几年来立体控制性合成含手性磷酸酯基的寡核苷酸类似物的进展, 重点介绍了寡核苷酸硫代磷酸酯和甲基膦酸酯的立体控制性合成方法 .     

Theoretical and structural studies on mechanism of the Stec reaction

The mechanism of the Stec reaction between phosphoroselenanilidate or phosphonoanilidate and CS₂, activated by strong bases, has been studied computationally, using DFT methods, and experimentally, by low temperature ³¹P NMR spectroscopy. From molecular calculations, the reaction pathway of the reaction has been revealed with several transition states and intermediates, including a low energy spirocyclic pentacoordinate transition state and acyclic tetracoordinate intermediates, which eventually were correlated with short living molecules detected by NMR spectroscopy.     

The reaction of dichlorocarbene with β-ethanolamines stereospecific synthesis of epoxides

Optically pure β-ethanolamines were converted into epoxides in good yield and with high e.e. ( ?, 95%) by reaction with dichlorocarbene. By this method α-aminoacids were successfully converted into synthetically useful epoxides.     

The synthesis of P-chiral amino acid-derived phosphonamidic anhydrides

The synthesis of an array of P-chiral amino acid-derived phosphonamidic anhydrides is described. These anhydrides are prepared by condensation of allylated amino acids 19-22 with methyl- or vinylphosphonic dichlorides 23 or 24 to produce three diastereomeric anhydrides 4-11a-c in good to excellent yields. The mechanistic issues concerning anhydride formation are discussed and supported by experimental results. Vinylphosphonamidic anhydrides 8-11 are further derivatized via the ring-closing metathesis (RCM) reaction to yield amino acid-derived bicyclic phosphonamidic anhydrides.     

A stereospecific synthesis of conjugated fluorodienes by a ring-opening reaction of gem-difluorocyclopropane derivatives

Ring-opening reactions of trans- and cis-gem-difluorocyclopropane derivatives (1) with appropriate bases proceeded stereospecifically to give (E, E)- and (E, Z)-fluorodiene derivatives (2), respectively.     

The stereospecific synthesis of spectinomycin

The first synthesis of spectinomycin, a complex and sensitive antibiotic, is described. The synthesis, which requires only four steps from known materials, has flexibility for modifying either half of the molecule.     

Efficient synthesis of cephalotaxine- and deoxyharringtonine analogues by a trimethylaluminium-mediated domino reaction

The synthesis of cephalotaxine- and cephalotaxine amide analogues 14a-c and 16a-c as well as of the deoxyharringtonine analogues 5a,b was performed employing a trimethylaluminium-mediated domino reaction of 9a-c and 8 to give the spirocyclic compounds 7a-c, which was followed by a palladium catalyzed α-arylation.     

A new approach to stereospecific synthesis of P-chiral phosphorothioates. Preparation of diastereomeric dithymidyl-(3'-5') phosphorothioates

A new method for stereospecific synthesis of P-chiral phosphorothioates based on intramolecular nucleophile catalysis was developed.     

Oxazolidine synthesis by complementary stereospecific and stereoconvergent methods

Complementary stereospecific and stereoconvergent reactions for enantioselective synthesis of 1,3-oxazolidines are reported. In the presence of a rhodium catalyst, reaction of enantioenriched butadiene monoxide with aryl imines is stereospecific (99% ee). Alternatively, the reaction of racemic butadiene monoxide, in the presence of a chiral palladium or nickel catalyst, provides an enantioselective synthesis of 1,3-oxazolidines (up to 94% ee). Synthesis of either the cis- or trans-1,3-oxazolidines is also accomplished under catalyst control.     

Vinyliodonium salts : their stereospecific synthesis and reactions as the activated vinyl halides

Vinyliodonium salts $\text{2}$ were synthesized from vinylsilanes $\text{1}$ by the reaction with iodosylbenzene and triethyloxonium tetrafluoroborate. The reaction occurs stereospecifically with retention of configuration. Vinyliodonium salts $\text{2}$ are highly effective as the activated species of vinyl iodides. Thus, a variety of substituted olefins including α-cyano and α-nitro olefins, vinyl sulfides, vinyl halides, and α,β-unsaturated esters, were prepared from $\text{2}$ under mild reaction conditions.     

Asymmetric synthesis of enantiomerically pure zingerols by lipase-catalyzed transesterification and efficient synthesis of their analogues

The achiral zingerone 1, readily available from ginger, can be easily transformed into chiral derivatives. Zingerol 2, a reduced product of zingerone 1 is expected to be an important new medicinal lead compound. We have achieved a concise synthesis of optically active zingerol (R)-2 and (S)-2 by the lipase-catalyzed stereoselective transesterification of racemic 2. Under the optimized conditions, a lipase from Alcaligenes sp. (Meito QLM) and vinyl acetate in i-Pr₂O or hexane at 35 °C within 1 h gave the alcohol (S)-2 and the acetate (R)-9 with high enantioselectivity without producing acetylated by-products. Since optically active (S)-2 and (R)-9 were obtained through lipase-catalyzed transesterification, other enantiomerically pure novel compounds could all be synthesized.     

The Kulinkovich reaction in the synthesis of constrained n,n-dialkyl neurotransmitter analogues

An intermolecular Ti(IV)-mediated cyclopropanation reaction has been used to synthesize substituted 2-phenylcyclopropylamines and constrained analogues of the neurotransmitters histamine and tryptamine. Many hydroxy- and methoxy-substituted phenylcyclopropylamines are known to inhibit monoamine oxidase and have been shown to mimic hallucinogens. These compounds were made in 1 to 5 steps from readily available starting materials.     

An application of the ireland reaction to the stereospecific synthesis of fused carbocyclic systems.

The sequence: group transfer Michael addition, aldol / lactonization and Claisen rearrangement provides access to the title compounds.     

Palladium-catalyzed stereospecific synthesis of 2,6-disubstituted tetrahydropyrans: 1,3-chirality transfer by an intramolecular oxypalladation reaction

PdCl2(CH3CN)2 (10 mol %) catalyzed reactions of non-3-ene-2,8-diols 1 and 2 gave 2,6-disubstituted tetrahydropyrans 3 and 4 in excellent yields with high diastereoselectivities (>20:1). Intramolecular cyclizations of the hydroxy nucleophile to the chiral allylic alcohol take place efficiently under mild conditions. A new stereogenic center is generated on the tetrahydropyran ring by 1,3-chirality transfer from the chiral allylic alcohol via a syn-SN2' type process. Cis tetrahydropyran 3E was formed from syn-2,8-diols 1a and 2a, and trans tetrahydropyran 4E was formed from anti-2,8-diol 1b, stereospecifically. Cis tetrahydropyran bearing a cis alkene 3Z was obtained from 2b at -40 degrees C, while 4E was formed from 2b in the presence of catalytic amount of water at -40 degrees C. The face selectivity of these cyclizations can be rationalized by taking a favorable conformation of the intermediary Pd pi-complex with allylic alcohols, escaping the allylic strain and 1,3-diaxial interactions. A stereocontrolled synthesis of optically pure 2-alkenyl-6-methyltetrahydropyran 17 was achieved efficiently in four steps from 6-silyloxy-1-heptyne 13 with an aldehyde and included asymmetric alkynylation, partial reduction of alkyne, deprotection of the silyl group, and the stereospecific cyclization.     

Total synthesis of ibogaine,epiibogaine and their analogues

Efficient total synthesis of ibogaine, epiibogaine and their analogues has been described. An intramolecular reductive-Heck type cyclization was used for the construction of seven-membered indoloazepine ring to access iboga-skeleton. Larock’s heteroannulation reaction was employed for the creation of suitably substituted indole and Diels–Alder reaction was employed for the construction of the isoquinuclidine ring present in iboga alkaloids.     

Synthesis of stereospecific hinged ladder polyimides by Diels-Alder reaction

A one-stage synthesis of hinge-ladder polyimides by Diels-Alder poly-condensation of polychlorinated cyclic bisimidodienes with bismaleimides containing aromatic and aliphatic groups was studied.