Stereoselective synthesis of 4 alpha-hydroxy-8,12-guaianolides from santonin

Hydroxyester 2, easily obtained from santonin (1), has been transformed into 10 alpha-hydroxyguai-3-en-8,12-olide 6, a good intermediate for the synthesis of natural 8,12-guaianolides. Compound 6 was obtained from 2 by photochemical rearrangement of its acetyl derivative 7, stereoselective hydrogenation on Pd/C, reduction, regioselective elimination, hydrolysis, and lactonization. The synthesis of the natural guaianolides 3-5 was carried out in two sequences in which the regioselective elimination of a hydroxyl group at C10 with triflic anhydride or SOCl2 to afford, respectively, the endo or exo double bond on C10 and the regioselective opening of the C3-C4 alpha-epoxide were the key steps.     

Regioselective synthesis of 3-arylamino- and 5-arylaminoisoxazoles from enaminones

A highly regioselective synthesis of 3-arylamino- and 5-arylaminoisoxazoles from enaminones based on reaction condition selection is reported. 3-Arylaminoisoxazoles were produced by treating enaminones with aqueous hydroxylamine in DMF at 100 °C, whereas 5-arylaminoisoxazoles were synthesized by subjecting enaminones to aqueous hydroxylamine in the presence of KOH and TBAB in water under reflux. A mechanism for the regioselective synthesis of 3-arylamino- and 5-arylaminoisoxazoles is proposed.     

New concept for the separation of an anomeric mixture of alpha/beta-D-nucleosides through regioselective enzymatic acylation or hydrolysis processes

An efficient and high yield protocol for the synthesis and separation of 3'- and/or 5'-protected alpha-2'-deoxynucleosides has been developed through regioselective acylation/deacylation processes catalyzed by enzymes. Pseudomonas cepacia lipase (PSL-C) was found to be highly chemo- and regioselective toward the 3'-position of the beta-2'-deoxynucleoside derivatives, whereas PSL-C displayed opposite selectivity toward the 5'-position for the corresponding alpha-anomer. The successful application of this protocol was demonstrated by a convenient separation of an alpha/beta-mixture of thymidine derivatives from an industrial waste stream. Furthermore, this technique was also applied for the separation of an anomeric mixture of 2'-deoxy-2'-fluoro-alpha/beta-arabinonucleosides that are useful building blocks for the antisense constructs.     

Total synthesis of (±)-heliannuol C and E via aromatic Claisen rearrangement

The total synthesis of heliannuol C and E from a common intermediate are described. Key steps in the synthesis include a regioselective aromatic Claisen rearrangement to install the (1-vinyl)-4-methyl-3-pentenyl substituent and regioselective biomimetic 7-endo and 6-exo phenol epoxide cyclizations to form the cyclic ether moieties.     

Palladium-catalyzed regioselective arylation of imidazo[1,2-b][1,2,4]triazine: synthesis of an alpha 2/3-selective GABA agonist

A convergent, practical, and efficient synthesis of 2',6-difluoro-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile (1), an orally active GABA(A) alpha(2/3)-selective agonist, is described. The seven-step, chromatography-free synthesis was demonstrated on a multi-kilogram scale and utilized biaryl bromide 6 and imidazotriazine 22 as key intermediates. Biaryl bromide 6 was prepared via a highly selective aromatic bromination. The regioselective condensation of aminotriazine 15 with chloroacetaldehyde provided the desired imidazotriazine intermediate 22. A highly regioselective palladium-catalyzed arylation in the final step highlights the efficiency of the route.     

Highly regioselective synthesis of trisubstituted allenes via lithiation of 1-aryl-3-alkylpropadiene, subsequent transmetalation, and Pd-catalyzed Negishi coupling reaction

A novel methodology for the synthesis of trisubstituted allenes is reported. Lithiation of 1-aryl-3-alkylpropadienes and subsequent transmetalation with zinc bromide followed by Pd-catalyzed Negishi coupling reactions with halides afforded the corresponding trisubstituted allenes in a highly regioselective fashion with moderate to excellent yields. A plausible regioselective lithiation mechanism was proposed on the basis of deuterium labeling experiments.     

The first total synthesis of potent human chymase inhibitor SPF32629B via regioselective bromination and O-acylation strategy

An efficient total synthesis of (±)-SPF32629B is described. The key features of the synthesis include regioselective bromination followed by carboxylation at C-3 and protecting-group-free regioselective acylation of hydroxyl group present at C7. Structure was determined by X-ray analysis.     

Highly stereo- and regioselective synthesis of a phenylene–silylene–vinylene polymer via ruthenium-catalyzed polycondensation

[RuCl₂(CO)₃]₂ catalyzed cross-coupling polycondensation of 1,4-bis(vinyldimethylsilyl)benzene (A) appears to be a new, very efficient, method for highly stereo- and regioselective synthesis of phenylene–silylene–vinylene polymers (B).     

Building blocks for the solution phase synthesis of oligonucleotides: regioselective hydrolysis of 3',5'-Di-O-levulinylnucleosides using an enzymatic approach

A short and convenient synthesis of 3'- and 5'-O-levulinyl-2'-deoxynucleosides has been developed from the corresponding 3',5'-di-O-levulinyl derivatives by regioselective enzymatic hydrolysis, avoiding several tedious chemical protection/deprotection steps. Thus, Candida antartica lipase B (CAL-B) was found to selectively hydrolyze the 5'-levulinate esters, furnishing 3'-O-levulinyl-2'-deoxynucleosides 3 in >80% isolated yields. On the other hand, immobilized Pseudomonas cepacia lipase (PSL-C) and Candida antarctica lipase A (CAL-A) exhibit the opposite selectivity toward the hydrolysis at the 3'-position, affording 5'-O-levulinyl derivatives 4 in >70% yields. A similar hydrolysis procedure was successfully extended to the synthesis of 3'- and 5'-O-levulinyl-protected 2'-O-alkylribonucleosides 7 and 8. This work demonstrates for the first time application of commercial CAL-B and PSL-C toward regioselective hydrolysis of levulinyl esters with excellent selectivity and yields. It is noteworthy that protected cytidine and adenosine base derivatives were not adequate substrates for the enzymatic hydrolysis with CAL-B, whereas PSL-C was able to accommodate protected bases during selective hydrolysis. In addition, we report an improved synthesis of dilevulinyl esters using a polymer-bound carbodiimide as a replacement for dicyclohexylcarbodiimide (DCC), thus considerably simplifying the workup for esterification reactions.     

Facile Synthesis of Unsymmetrical N-Aryl-2, 2-di(1H-indol-3-yl) Acetamide Derivatives

A facile and highly efficient method has been developed for the synthesis of unsymmetrical N-aryl-2,2-di(1H-indol-3-yl)acetamide derivatives by regioselective Friedel-Crafts alkylation of the N-aryl-2-hydroxy-2-(1H-indol-3-yl) acetamide derivatives with various indoles catalyzed by 2 mol/L H₂SO₄ at room temperature in a short reaction time, the yield was up to 94%.     

Diversity-oriented regioselective domino Michael/Aldol reaction of 3-ylideneoxindoles: A direct access to indanol-fused 3-oxindoles

A diversity-oriented molecular hybridization strategy has been utilized for the synthesis of 2,3-disubstituted 1-indanol-fused 3-oxindoles through a regioselective domino Michael/Aldol reaction of 3-ylideneoxindoles 1 with malononitrile or cyanacetate ethyle 2. Products bearing consecutive stereocenters consist of an oxindole moiety and an indanol core, were smoothly obtained in high yields (up to 92% yield) with good diastereoselectivity (up to 20:1). This protocol also represents the first construction of indanol-fused 3-oxindole scaffolds, thus leading to new knowledge in the fields of both molecular complexity and diversity-oriented synthesis (DOS) and the lead compound discovery. It is also worth mentioning that the reaction was completely regioselective and the competitive regioisomeric products 4 or 5 were not obtained in any case.     

Palladium-catalyzed domino protodecarboxylation/oxidative Heck reaction: regioselective arylation of coumarin-3-carboxylic acids

A protocol for straightforward and step-economical synthesis of neoflavones from coumarin-3-carboxylic acids is developed. This approach enables controlled protodecarboxylation/regioselective C–H arylation of coumain-3-carboxylic acids in one-pot using a monometallic catalytic system. A wide variety of electron-donating and -withdrawing substituents on both coumarins and arylboronic acid are tolerated under the reaction conditions and 4-aryl coumarins are constructed in high yields.     

3-Halotetrahydropyran-4-one Derivatives from Homopropargyl Acetal

A gold(I)-catalyzed regioselective method for the preparation of 3-bromo/iodo-tetrahydropyran-4-one derivatives from homopropargyl acetal is reported. A one-pot procedure based on a gold(I)-catalyzed Petasis–Ferrier rearrangement/cyclization and subsequent electrophilic halogenation was developed. Corresponding hemiacetals were not suitable substrates for the formation of the 3-halo-pyran derivatives. The present transformation is a useful method to readily afford highly substituted 3-halo-tetrahydropyran-4-ones, which are suitable substrates in a variety of reactions in further synthesis.     

蔗糖酯的酶催化区域选择性合成

酶可以区域选择性地合成蔗糖酯，枯草杆菌等蛋白酶被用来区域选择性合成 1'-O-蔗糖酯，且通常不接受长链（大于C_(12))脂肪酸作为酰基授体，而脂肪酶可 催化宽范围的脂肪酸，除了脂肪酶和蛋白酶外，研究发现抗体酶也能区域和立体选 择地酰化蔗糖。蔗糖二酯、线型蔗糖酯都可以通过酶催化区域选择性地合成。酶催 化合成蔗糖酯通常在二甲基甲酰胺、二甲基亚砜和吡啶等有毒溶剂中进行。近几年 来，无溶剂条件下酶催化合成蔗糖酯，以及用叔丁醇等毒性较小的溶剂代替毒性较 大的溶剂的研究，也越来越受重视。     

First total synthesis of （±）-malaysianone A and （±）-tanariflavanones B

A concise approach for the frst total synthesis of two naturally occurring flavanoids,（）-malaysianone A（1）and（）-tanariflavanones B（2）,has been accomplished with total yields of 12.9%and 10.4%,respectively.The key steps were regioselective deprotection and regioselective synthesis of 5-formaldehyde-8-hydroxy-2-[40-methyl-30-penteneyl]-dihydro-1-benzopyran（8）.     

One-pot synthesis of β-hydroxysulfides from styrenes and disulfides using the Zn/AlCl3 system

A simple, general, and highly regioselective procedure has been developed for the one-pot synthesis of β-hydroxysulfides in good yields from various styrenes and disulfides by cleavage of the S-S bond with a Zn/AlCl₃ system in aqueous acetonitrile at 80 °C and in the presence of oxygen.     

Total synthesis of diptoindonesin G via a highly efficient domino cyclodehydration/intramolecular Friedel-Crafts acylation/regioselective demethylation sequence

A highly efficient total synthesis of diptoindonesin G is described employing a domino dehydrative cyclization/intramolecular Friedel-Crafts acylation/regioselective demethylation reaction of aryloxyketone 7 by the action of BCl(3) wherein the tetracyclic 6H-anthra[1,9-bc]furan-6-one skeleton was constructed via the 3-arylbenzofuran in a one-pot manner. This is the first example of the strategic combination of these three reactions in a cascade fashion. The routes presented here allow for direct access to diptoindonesin G and its analogues.     

A Simple and Efficient Regioselective and Chemoselective Synthesis of New Substituted 3‐Methyl‐6‐arylpyridazine‐4‐carboxamides and 5‐Oxo‐3‐aryl‐5,6‐dihydropyrido[4,3‐c]pyridazine‐8‐carbaldehydes

A facile, green, and one‐pot approach is described for the regioselective synthesis of new substituted 3‐methyl‐6‐arylpyridazine‐4‐carboxamides in water at room temperature. Subsequent treatment of these products with the Vilsmeier reagent led to chemoselective and regioselective production of new 5‐oxo‐3‐aryl‐5,6‐dihydropyrido[4,3‐c]pyridazine‐8‐carbaldehydes in good to excellent yields.     

Regioselective synthesis of 1-aryl-3,4-substituted/annulated-5-(methylthio)pyrazoles and 1-aryl-3-(methylthio)-4,5-substituted/annulated pyrazoles

[reaction: see text] Highly efficient and regioselective synthesis of 1-aryl-3,4-substituted/annulated-5-(methylthio)pyrazoles and 1-aryl-3-(methylthio)-4,5-substituted/annulated pyrazoles has been reported via cyclocondensation of arylhydrazines with either alpha-oxoketene dithioacetals or beta-oxodithioesters.     

Synthesis of Lapatinib via direct regioselective arylation of furfural

A new synthesis of Lapatinib, an orally active drug for breast cancer, is described. The synthesis involves a palladium catalyzed regioselective arylation of furfural with 6-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)quinazolin-4-amine. This key step replaces an atom inefficient Suzuki cross coupling reaction used in a previously disclosed route and significantly shortens the synthesis.