Synthetic studies on neomarinone: practical and efficient stereoselective synthesis of the side chain

A practical and efficient stereoselective synthesis of the side chain of neomarinone is reported. The synthesis was achieved in six steps (41% overall yield) from 2-methyl-2-cyclohexenone. The key step is a novel stereoselective 1,4-conjugate addition/enolate alkylation by an epoxide-opening reaction.     

2-Isopropylbenzimidazole and 2-methylbenzimidazole as bulky proton sources: Stereoselective protonation and application to the synthesis of γ- and δ-lactones

2-Isopropylbenzimidazole and 2-methylbenzimidazole have been found to be effective bulky proton sources for stereoselective protonation of chiral enolate anions. 2-Isopropylbenzimidazole worked in the stereoselective protonation of the Birch reduction of chiral α,β-unsaturated imides. On the other hand, 2-methylbenzimidazole was found to be the best protonation reagent in the isomerization reaction of α,β-unsaturated imide into β,γ-unsaturated imide. The Birch reduction using 2-isopropylbenzimidazole realized a concise and stereoselective synthesis of δ-lactone 14, a sex pheromone of Macrocentrus grandii, while the isomerization reaction using 2-methylbenzimidazole was employed in the highly stereoselective synthesis of the γ-lactone intermediate in the synthesis of depsipeptide antibiotics. These bulky proton sources would be powerful tools to achieve a concise synthesis of natural products.     

Regioselective epoxide ring opening. Steroselective synthesis of a tetrahydropyran ring

The stereoselective synthesis of a 2-substituted tetrahydropyran with adjacent alkoxy-bearing stereogenic centre is described. The key steps of this synthesis were the stereoselective epoxidation of an allylic alcohol and the regioselective epoxide ring opening by lithium aluminum hydride. The regio and stereoselective synthesis of a trihydroxyselenide and a trihydroxysulfide is also described. The latter compounds are not suitable for cyclization to tetrahydrofuran ring.     

P-heterocyclic building blocks: application to the stereoselective synthesis of P-sugars

A strategy relying on the utilization of stereoselective additions to allyldiphenylphosphonate esters and subsequent ring-closing metathesis (RCM) to access P-chiral P-heterocyclic building blocks for the synthesis of phosphono sugars is described. These building blocks possess several attractive components, including the following: (i) P(2) and C(6) stereogenic centers for directing stereoselective transformations; (ii) an activated C(3) methylene group that promotes base-mediated olefin transposition to generate vinyl phosphonates available for further stereoselective reactions; and (iii) a P(2)-stereogenic center containing an exchangeable phosphonate ester armed to attenuate the "stereochemical environment" at phosphorus. Taken collectively, these attributes contribute to a concise method for the stereoselective synthesis of an array of P-sugars.     

A stereoselective route toward polyhydoxylated piperidines. A total synthesis of (+/-)-deoxymannojirimycin

[reaction: see text] A chemo- and stereoselective palladium-catalyzed amination of silylated butenediol dicarbonates has allowed for the introduction of a glycine moiety to obtain a desired functionalized epoxysilane. A stereoselective aldolization then delivered the piperidine ring which may be used as a precursor for the synthesis of a variety of polyhydroxylated azasugars. This efficient approach has been illustrated by the synthesis of 1-deoxymannojirimycin including a stereoselective reduction with LAH and a Tamao-Fleming oxidation of a C-SiMe(2)Ph bond.     

Synthesis of renieramycins: construction of the core ring system of cribrostatin 4 through modified Pictet-Spengler cyclization of 3,6-bisarylpiperazine-2,5-dione with diethoxyethyl benzoate

A nine-step synthesis of pentacyclic key intermediate 11 of cribrostatin 4 (2) along with renieramycin I (1i) from 3,6-bisarylpiperazine-2,5-dione derivative 3 is described. The key step of this synthesis is the stereoselective cyclization of lactam nitrogen with diethoxyethyl benzoate, followed by the stereoselective hydrogenation to generate ABC ring system 6.     

Synthetic studies on (+)-naphthyridinomycin: stereoselective synthesis of the tetracyclic core framework

[reaction: see text] The stereoselective synthesis of the tetracyclic intermediate 21 for (+)-naphthyridinomycin (1) has been accomplished. The convergent synthesis used the Ugi 4CC reaction with the amine derivative 10. The key features of the stereoselective synthesis of 21 were the intramolecular Mizoroki-Heck reaction, an aromatic-aldehyde cyclization, and a stereoselective hydroboration.     

Stereoselective Total Synthesis of Crassalactone A,a Natural Cytotoxic Styryl Lactone

A stereoselective total synthesis of a naturally occurring cytotoxic styryl lactone, crassalactone A ( 1 ), has been accomplished. The synthesis involves (?)‐diisopropyl D ‐tartrate as the starting material, and the stereoselective additions of Grignard reagent and MeNO₂ to two chiral aldehyde intermediates as the key steps.     

New reactions of alkynes with ketones in superbasic media

The present work reviews new reactions of alkynes with ketones in the superbasic media MOH—DMSO (M = Na, K, Cs) and KOBu^t—DMSO: the stereoselective nucleophilic addition of deprotonated ketones to the triple bond to form the E-isomers of β,γ-enones; vinylation of tertiary acetylenic alcohols that formed in situ from acetylene and ketones; the direct synthesis of vinyl ethers of tertiary acetylenic alcohols from acetylene and ketones; the stereoselective synthesis of dispirocyclic ketals containing the Z-ethylene fragment from arylalkynes and two molecules of a cyclic ketone; the stereoselective cascade synthesis of hexahydroazulenones from two arylalkyne molecules and 2-alkylcyclohexanones; the stereoselective cascade assembly of 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes from two acetylene molecules and two ketone molecules; the stereoselective cascade synthesis of 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes from acetylenes and 1,5-diketones; and the three-component cascade reaction of acetylene, ketones, and oximes to afford 4-methylidene-3-oxa-1-azabicyclo-[3.1.0]hexanes.     

The Stereoselective Synthesis of Disubstituted E,Z-Diene Ester

The new method for the stereoselective synthesis of disubstituted diene ester was successfully applied to a highly stereoselective synthesis of E, Z-diene ester (1).     

The total synthesis of (±)-naphthyridinomycin. II. Construction of the pentacyclic carbon skeleton.

A synthesis of an advanced pentacyclic intermediate to the quinone antibiotic naphthyridinomycin (1) is described. The stereoselective synthesis of 2b from tricyclic lactam 3¹ features a regio- and stereoselective, intermolecular amidoalkylation reaction and a Friedel-Crafts ring closure to annelate the aromatic nucleus.     

A concise stereoselective route to the indoline spiroaminal framework of neoxaline and oxaline

The stereoselective synthesis of tetracyclic intermediate, the indoline spiroaminal 3 for neoxaline (1) and oxaline (2), has been accomplished. The key step of the stereoselective synthesis of 3 was the Lewis acid mediated transcyclization of 4 to the diaminal 18, and the tungstate-catalyzed oxidation of 18 to obtain the nitrone 19, which easily cyclizes to the indoline spiroaminal framework 3. [structure: see text]     

Total synthesis of (−)-funebrine via Au-catalyzed regio- and stereoselective γ-butyrolactonization of allenylsilane

The stereoselective total synthesis of (−)-funebrine from 2-butyn-1-ol was described. The crucial steps in the synthesis involved the stereoselective enolate Claisen rearrangement of the (S)-α-acyloxy-α-alkynylsilane 8, the Au-catalyzed regio- and stereoselective lactonization of the allenylsilane 7, and the Paal-Knorr pyrrole condensation using an unsymmetrical 1,4-diketone 4b.     

Tandem overman rearrangement and intramolecular amidomercuration reactions. stereocontrolled synthesis of cis- and trans-2,6-dialkylpiperidines

[reaction: see text] Hg(II)-mediated tandem Overman rearrangement and intramolecular amidomercuration reactions were proven to provide a convenient tool for the stereoselective synthesis of cis- and trans-2,6-disubstituted piperidines. Thus, upon treatment with Hg(OTFA)(2) in THF, the trichloroacetimidate 1 directly transformed into the 2,6-dialkyl piperidine 2 with almost exclusive trans selectivity. The amiodomercuration reaction of the carbamate 7 by Hg(OTFA)(2) in nitromethane showed an excellent cis selectivity. Also reported is the stereoselective synthesis of solenopsin A and isosolenopsin A.     

Stereoselective oxidative rearrangement of 2-aryl tryptamine derivatives

The oxidation of 2-aryl tryptamines followed by a stereoselective rearrangement provides a versatile strategy for the synthesis of C3-quaternary oxindoles bearing a C3-aryl group. Treatment of optically active 2-aryl hydroxyindolenines with scandium trifluoromethanesulfonate in toluene at 110 degrees C leads to complete and stereoselective isomerization to the corresponding C3-aryl oxindoles which represent versatile intermediates for the synthesis of C3a-aryl hexahydropyrroloindoles.     

The sulfinyl moiety as an internal nucleophile. 2. Stereoselective synthesis of (-)-galantinic acid via 1,3-asymmetric induction

A stereoselective synthesis of (-)-galantinic acid is disclosed. The key steps include hydrolytic kinetic resolution of a racemic epoxide and regio- and stereoselective heterofunctionalization of an olefin, using a pendant sulfinyl group as the nucleophile. The participation of the sulfinyl group was unambiguously proven by conducting the reaction in the presence of H(2)(18)O.     

The first total synthesis of (+/-)-arisugacin A, a potent, orally bioavailable inhibitor of acetylcholinesterase

The first convergent total synthesis of (+/-)-arisugacin A was accomplished by stereoselective construction of the arisugacin skeleton via a Knoevenagel-type reaction of an alpha,beta-unsaturated aldehyde with a 4-hydroxy 2-pyrone and stereoselective dihydroxylation followed by deoxygenation.     

Total Synthesis of Antitumor Antibiotic Derhodinosylurdamycin A

The first total synthesis of derhodinosylurdamycin A, an angucycline antitumor antibiotic, has been described. The synthesis features a Hauser annulation followed by pinacol coupling to construct the tetracyclic angular aglycon, a Stille coupling of glycal stannane and tetracyclic aryliodide followed by stereoselective reduction to afford the 2‐deoxy β‐C‐arylglycoside, and a late‐stage stereoselective glycosylation for the preparation of derhodinosylurdamycin A. This synthetic strategy should be amenable to the chemical synthesis of analogs of derhodinosylurdamycin A bearing diverse 2‐deoxy sugar subunits for structure and activity relationship studies.     

Stereoselective synthesis of bis-β-lactam grafted macrocycles

The synthesis of a series of macrocyclic bis-β-lactam derivatives via a highly stereoselective (2+2) cycloaddition is described.     

4-Oxo-2-cyclopentenyl Acetate—A Synthetic Intermediate

The present day importance of cyclopentenone derivatives in preparative organic chemistry and especially in natural product chemistry is demonstrated by the stereoselective synthesis of substituted and annelated cyclopentanone derivatives. It has been found that 4-oxo-2-cyclopentenyl acetate (“4-acetoxy-2-cyclopenten-1-one”) can be used in many reactions as a substitute for cyclopentadienone, which is itself too unstable to be isolated. A large variety of polyfunctionalized cyclopentanone derivatives, as well as carbocyclic and heterocyclic annelation products, can thus be obtained in a simple way. Various stereoselective transformations of the adducts so formed are presented, using the total synthesis of brefeldin A—a typical natural product of this series—as example. Several methods for the synthesis of 4-oxo-2-cyclopentenyl acetate are outlined and, in addition, the more important methods for the enantioselective synthesis of other 4-substituted 2-cyclopenten-1-ones are discussed.