Diastereospecific Synthesis Research Articles

Green diastereospecific synthesis of various medicine analogues containing dipeptides and release of the medicines by Baker's yeast

We have succeeded green and economical synthesis of various dipeptides in 76–99% yields with 70–>99% de and dipeptides-containing medicine analogues in 74–99% yields with 79–97% de in aqueous THF at −15 °C via the mixed carbonic carboxylic anhydrides by the activation of the corresponding carboxylic acids. We observed that the anilide l-Phe-l-Phe-NHC6H4-4-OH, one of the deprotecting medicine analogues, was cleaved at the C-terminal of l-phenylalanine (l-Phe) by Baker's yeast under starvation conditions followed by treatment of a freshly prepared PhCH2CH2CO2CO2Et from 3-phenylpropanoic acid, ClCO2Et, and Et3N in MeCN to afford PhCH2CH2CONHC6H4-4-OH and PhCH2CH2CO-l-Phe-NHC6H4-4-OH in 46% and 42% yields, respectively. Interestingly, biocatalytic hydrolysis of l-Phe-d-Phe-NHC6H4-4-OH by Baker's yeast gave PhCH2CH2CO-d-Phe-NHC6H4-4-OH in 20% yield and PhCH2CH2CO-l-Phe-d-Phe-NHC6H4-4-OH 60% recovery yield.

FeCl3‐Catalyzed Highly Diastereoselective Synthesis of Polyhydrobenzo[a]acridinones

AbstractFeCl3‐catalyzed diastereospecific synthesis of tetrahydrobenzo[a]acridin‐5(6H)‐ones from enaminones was described. Single diastereoisomers were obtained in good to excellent yields. Two C−C bonds and three contiguous stereogenic centers were formed.

Green Diastereospecific Synthesis of Various Medicine Analogues Containing Dipeptides and Release of the Medicines by Baker's Yeast

Green Diastereospecific Synthesis of Various Medicine Analogues Containing Dipeptides and Release of the Medicines by Baker's Yeast

Diastereospecific Synthesis of Tetrahydroisoquinolines via Radical Cyclization: Application in the Synthesis of ent‐Tadalafil

AbstractAn enantioselective synthesis of 1‐substituted tetrahydroisoquinolines from L–Dopa methyl ester through intramolecular aryl radical cyclization is demonstrated. The strategy consists of bromination of (S)‐2‐amino‐3‐(2‐bromo‐4,5‐dimethoxyphenyl)propanoate followed by condensation with various aldehydes to afford bromoimidate ester. Aryl radicals generated from bromoimidate ester under the radical generating conditions (nBu3SnH/AIBN) cyclizes via 6‐endo mode to afford cis‐1‐substituted tetrahydroisoquinolines exclusively in 99% ee. The utility of this synthetic protocol is demonstrated in the synthesis of (6S, 12aS) Tadalafil (5 steps, 21%, 99% ee).magnified image

Transition metal-free diastereospecific synthesis of (Z)-2-arylidene-2,3-dihydrobenzo[b][1,4]dioxines by reaction of (Z)-1,2-dibromo-3-aryl-2-propenes with catechols

Abstract A transition metal-free, diastereospecific reaction between substituted (Z)-1,2-dibromo-3-phenyl-2-propenes and substituted catechols using Cs2CO3 as a base at 140 °C for 18 h delivers exclusively substituted (Z)-2-arylidene-2,3-dihydrobenzo[b][1,4]dioxines in yields up to 89%. Experiments as well as quantum chemical calculations support the assumption that the one pot transformation proceeds as an intermolecular O-allylation/intramolecular O-vinylation.

Triarylaminium Radical Cation Promoted Coupling of Catharanthine with Vindoline: Diastereospecific Synthesis of Anhydrovinblastine and Reaction Scope.

A new triarylaminium radical cation promoted coupling of catharanthine with vindoline is disclosed, enlisting tris(4-bromophenyl)aminium hexachlororantimonate (BAHA, 1.1 equiv) in aqueous 0.05 N HCl/trifluoroethanol (1-10:1) at room temperature (25 °C), that provides anhydrovinblastine in superb yield (85%) with complete control of the newly formed quaternary C16' stereochemistry. A definition of the scope of aromatic substrates that participate with catharanthine in the BAHA-mediated diastereoselective coupling reaction andsimplified indole substrates other than catharanthine that participate in the reaction are disclosed that identify the key structural features required for participation in the reaction, providing a generalized indole functionalization reaction that bears little structural relationship to catharanthine or vindoline.

Copper-Catalyzed Hydroalkylation of Terminal Alkynes

We have developed a copper-catalyzed hydroalkylation of terminal alkynes using alkyl triflates as coupling partners and (Me(2)HSi)(2)O as a hydride donor. The hydroalkylation proceeds with excellent anti-Markovnikov regioselectivity and provides exclusively (E)-alkenes. We have demonstrated that both alkyl- and aryl-substituted alkynes can be used as substrates, together with 1° alkyl and benzylic triflates. Finally, the transformation can be accomplished in the presence of a wide range of functional groups. Overall, the new hydroalkylation reaction allows highly efficient and diastereospecific synthesis of (E)-alkenes from readily available terminal alkynes and alkyl triflates. On the basis of a preliminary mechanistic study, we propose that the hydroalkylation reaction involves copper hydride formation, hydrocupration of an alkyne, and alkylation of an alkenyl copper intermediate.

Distal two-bond versus three-bond electronegative oxo-substituent effect controls the kinetics and thermodynamics of the conversion of a C-nitroso function to the corresponding oxime in the conformationally locked pentofuranose (bicyclo[2.2.1]heptane) system.

We report the high-yielding and scalable diastereospecific synthesis of isomeric bicyclo[2.2.1]heptane-7- and -8-oximes and their corresponding C-nitroso derivatives, which are the key intermediates for the synthesis of carbanucleosides. Neither the (C7-R)-nitroso- nor (C8-S)-nitrosobicycloheptane system requires any external base in DMSO-d6 to afford the corresponding oxime, and no reverse isomerization from the oxime to the C-nitroso compound was observed. The conversion of the (C8-S)-nitroso compound to the E/Z-oximes was ∼8 times faster (at 40 °C) than that of the (C7-R)-nitroso derivative. The mechanism involves first-order reaction kinetics for the conversion of either the (C7-R)- or (C8-S)-nitroso derivative to the corresponding E/Z-oximes. The lower rate of conversion of the (C7-R)-nitroso compound to the corresponding oximes compared with that of the (C8-S)-nitroso derivative is attributed to the fact that the acidic H8 ionizing center is two bonds away from the OPMB group on C1 in the latter whereas H7 is three bonds away from the C1 OMe group in the former, making the effect of the electron-withdrawing group on C1 stronger in the latter.

Diastereospecific synthesis of new 4-substituted l-theanine derivatives

Considering the biological activity of l-theanine as a potent agonist of NMDA receptors, impacting on glutamatergic synapse activity, we have developed an asymmetric synthesis of new enantiomerically pure 4-substituted l-theanine derivatives. The key step is a stereospecific alkylation on a previously synthesized and correctly protected (S)-pyroglutamate.

Domino Carbopalladation‐Carbonylation: Investigation of Substrate Scope

AbstractThis work gives an in depth account of our domino carbopalladation‐carbonylation method for substrates possessing β‐hydrogens. The scope of the method is examined for allylic amines containing trisubstituted olefins and we detail our attempts toward the diastereospecific synthesis of contiguous quaternary centers using this technology. The results give key insights into the relative rates of the competing reactions of the alkyl palladium intermediates, which is crucial for the understanding and development of new domino processes.

ChemInform Abstract: Triphenylarsine as an Efficient Catalyst in Diastereospecific Synthesis of N‐Vinyl Heterocyclic Compounds.

AbstractA simple, mild, and effective one‐pot synthesis of the title compounds (III) is presented.

Triphenylarsine as an Efficient Catalyst in Diastereospecific Synthesis of N-Vinyl Heterocyclic Compounds

A diastereospecific synthesis of N-vinyl heterocyclic compounds is described from a reaction of dialkyl acetylenedicarboxylate and N-H heterocyclic compounds, such as phthalimide, saccharin, 3(2H)-pyridazinone, isatin, maleimide, 2,4-thiazolidinedione, 2-benzoxazolinione and 6-chloro-2-benzoxazolinione, in the presence of triphenylarsine as an efficient catalyst, in excellent yield. The presented one-pot method is simple and effective with mild conditions.

ChemInform Abstract: Diastereospecific Synthesis of D- and L-allo-Threonines and Trichlorinated Derivatives Suitable for the Preparation of Tritium Labelled Material.

Abstract D- or L- serine can be converted to L- or D-γ,γ,γ-trichloro- allo -treonine, which on catalytic hydrogenolysis give diastereochemistry pure L- allo -threonine respectively. This procedure can be adapted to the preparation of tritium labelled material. D- or L-serine can be converted to L- or D-γ,γ,γ-trichloro- allo -threonine, which on catalytic hydrogenolysis give diastereomerically pure L- allo or D- allo -threonine respectively. This procedure can be adapted to the preparation of tritium labelled material.

ChemInform Abstract: A Concise Diastereospecific Synthesis of 3-Amino-2-hydroxy Acids.

ChemInform Abstract: A Concise Diastereospecific Synthesis of 3-Amino-2-hydroxy Acids.

Synthetic mRNA Splicing Modulator Compounds with in Vivo Antitumor Activity

We report our progress on the development of new synthetic anticancer lead compounds that modulate the splicing of mRNA. We also report the synthesis and evaluation of new biologically active ester and carbamate analogues. Further, we describe initial animal studies demonstrating the antitumor efficacy of compound 5 in vivo. Additionally, we report the enantioselective and diastereospecific synthesis of a new 1,3-dioxane series of active analogues. We confirm that compound 5 inhibits the splicing of mRNA in cell-free nuclear extracts and in a cell-based dual-reporter mRNA splicing assay. In summary, we have developed totally synthetic novel spliceosome modulators as therapeutic lead compounds for a number of highly aggressive cancers. Future efforts will be directed toward the more complete optimization of these compounds as potential human therapeutics.

Diastereospecific synthesis of phosphinidene-capped cyclodextrins leading to "introverted" ligands.

alpha-Cyclodextrins (alpha-CDs) containing "PPh" units which cap the primary face of the CD were obtained in high yield by reaction of Li(2)PPh with A,B- or A,C-dimesylated and A,B,D,E-tetramesylated precursors; the resulting phosphines are diastereomerically pure and constitute valuable precursors for the synthesis of metallo-cavitands.

Diastereospecific synthesis of novel [3.6.6.4.7]-fused pentacyclic β-lactams by 6- exo- trig, 7- endo- dig tandem radical cyclization

An efficient synthesis of pentacyclic β-lactams has been achieved in high yield via a novel 6- exo- trig, 7- endo- dig tandem radical cyclization.

Diastereospecific synthesis of (S,S)‐2‐substituted‐4,4‐diphenyl‐3, 1‐oxazabicyclo[3.3.0]octanes

Abstract(S,S)‐2‐Substituted‐4,4‐diphenyl‐3,1‐oxazabicyclo[3.3.0]octanes were synthesized diaster‐eospecifically from aldehydes and (S)‐2‐(hydroxydiphenylmethyl)pyrrolidine, which was obtained from L‐proline, under acid‐catalyzed conditions in anhydrous toluene. The stereospecificity of the condensation reaction is discussed. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:42–45, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10064

Diastereospecific synthesis of novel tetracyclic β-lactams via 6 -exo-trig radical cyclization

An efficient and diastereospecific synthesis of a tetracyclic, 3.6.6.4 ring system fused to a β-lactam has been achieved in high yield via 6- exo-trig radical cyclization.

Diastereospecific synthesis of β-heterosubstituted alcohols from 1,2-diols via 1,3,2λ5-dioxaphospholanes

The stereochemistry of the ring opening of (R,S) or (R,R) -4,5-dimethyl-2,2,2-triphenyl-1,3,2λ 5 -dioxaphospholanes (prepared by reaction of (R,S) or (R,R) -butane-2,3-diol with dibromotriphenylphosphorane) by aniline or thiophenol was investigated. The reaction affords stereoselectively the corresponding β-anilino- or β-phenylthioalcohols with a nearly complete inversion of stereochemistry at the stereogenic reaction centre. La stéréochimie des réactions d’ouverture des cycles (R,S) ou (R,R) -4,5-diméthyl-2,2,2-triphényl-1,3,2λ 5 -dioxaphospholanes (préparés à partir du (R,S) ou (R,R) -butane-2,3-diol et du dibromotriphénylphosphorane) par l’aniline ou le thiophénol a été étudiée. La réaction donne stéréosélectivement les β-anilino- or β-phénylthioalcools correspondants, avec une inversion presque totale de stéréochimie sur le centre réactif stéréogénique.