Ethynyl MIDA boronate: a readily accessible and highly versatile building block for small molecule synthesis

Ethynyl N-methyliminodiacetic acid (MIDA) boronate is a very useful building block for small molecule synthesis. This compound can serve as both a bifunctional acetylene equivalent with the capacity for terminus-selective bis-functionalization and a versatile starting material for the preparation of a wide range of other MIDA boronate building blocks.     

Vinyl MIDA boronate: a readily accessible and highly versatile building block for small molecule synthesis

Iterative cross-coupling represents a potentially general approach for the simple, efficient, and flexible construction of natural products, pharmaceuticals, and materials. N-Methyliminodiacetic acid (MIDA) boronates represent a promising platform for the development of this type of synthesis strategy. This report describes the discovery that vinyl MIDA boronate (1) is an air- and chromatographically stable compound that can be conveniently prepared on a multigram scale and serve as a versatile starting material for the preparation of a range of new MIDA boronate building blocks. Analogous to tert-butylethylene, 1 is also an excellent substrate for olefin cross-metathesis, providing access to a range of trans-alkenyl MIDA boronates as single stereoisomers. An improved synthesis of the very versatile bifunctional building block trans-(2-bromovinyl) MIDA boronate (2) is also described. Collectively, these results contribute to the expanding generality of the iterative cross-coupling approach.     

Polymer-supported thioanisole: a versatile platform for organic synthesis reagents

A new cross-linked polystyrene-supported thioanisole reagent is reported. This reagent incorporates the flexible JandaJel™ cross-linker and can be treated with methyl trifluoromethanesulfonate to form the corresponding sulfonium salt. This salt can in turn be deprotonated to form a polymer-supported sulfur ylide that is able to react with aldehydes and ketones to form epoxides. The thioanisole reagent can also be oxidized to form an insoluble sulfoxide reagent that is useful in Swern oxidation reactions. In these reactions, the polymer-supported thioanisole-based reagents can be recovered, regenerated and reused.     

A concise synthesis of (±)-3-deoxyisoaltholactone

The novel styryl lactone analog (±)-3-deoxyisoaltholactone was synthesized in 5 steps from dihydrofuran. An intramolecular vinylsilane–oxocarbenium condensation thus afforded the central cis-fused bicyclic ether array in near quantitative yield as a single stereoisomer.     

PTSA catalyzed straightforward protocol for the synthesis of 2-(N-acyl)aminobenzimidazoles and 2-(N-acyl)aminobenzothiazoles in PEG

An efficient PTSA catalyzed synthesis of 2-(N-acyl)aminobenzimidazoles and 2-(N-acyl)aminobenzothiazoles has been described using S-ethylated-N-acylthioureas as substrates and polyethylene glycol as solvent.     

Alternative approaches to (Z)-1,2-bis(2-bromopyridin-3-yl)ethenes, key intermediates in the synthesis of the 1,10-phenanthroline core

A study on the synthesis of (Z)-1,2-bis(2-bromopyridin-3-yl)ethenes, key intermediates in the preparation of 1,10-phenanthrolines, based on selective Sonogashira and Suzuki-Miyaura cross-coupling reactions has been carried out.     

Biomimetically inspired total synthesis of (12S)-12-hydroxymonocerin and (12R)-12-hydroxymonocerin

A concise asymmetric total synthesis of (12S)-12-hydroxymonocerin (1) and (12R)-12-hydroxymonocerin (2) were efficiently achieved from the known 4-bromo-2,6-dimethoxyphenol. The synthetic approach was inspired by our biomimetic synthesis of (+)-monocerin (3) and 7-O-demethylmonocerin (4). The cis-fused furobenzopyranones of 1 and 2 was efficiently constructed via an intramolecular nucleophilic trapping of a quinonemethide intermediate, which was obtained by benzylic oxidation of compound 10 using 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).     

A highly efficient stereoselective synthesis of (Z)- and (E)-allyl iodides from Baylis-Hillman adducts

A highly efficient synthesis of (Z)- and (E)-allyl iodides has been accomplished by treatment of Baylis-Hillman adducts with iodine and triphenylphosphine in methylene chloride at room temperature. The method is associated with mild reaction conditions, high yields and excellent stereoselectivity.     

Synthesis and characterization of a new boronate affinity monolithic capillary for specific capture of cis-diol-containing compounds

Boronate affinity chromatography (BAC) is an important tool for specific capture and separation of cis-diol-containing compounds such as glycoproteins, RNA and carbohydrates. Only a few reports on monolithic column-based BAC have appeared. In this paper, boronate functionalized monolithic capillary column was synthesized by in situ free radical polymerization for the first time. The prepared column was first characterized in terms of morphology, pore properties, capacity and retention mechanisms. The column exhibited uniform open channel network and high capture capacity. Systematical investigation on the retention mechanism revealed that multiple intermolecular interactions occur between the analytes and the boronate affinity monolith, including boronate affinity, reversed-phase, cation-exchange and hydrogen bonding interactions, depending on the conditions used. In addition, the presence of Lewis base such as fluoride ion in the mobile phase was found to be favorable to the complexation between cis-diol-containing compounds with the boronic acid ligand under less basic conditions. On the basis of these fundamental investigations, the prepared monolithic column was then applied to the capture of adenosine and flavin adenine dinucleotide. The investigations in this study provide sound understanding not only on how to manipulate the separation selectivity through selection of appropriate mobile phase composition on the currently prepared columns but also on how to design next-generation columns with desired properties and functions.     

A new titanate/(+)-(1R,2S)-cis-1-amino-2-indanol system for the asymmetric synthesis of (S)-tenatoprazole

Tenatoprazole, a substituted imidazopyridinyl derivative, is an irreversible proton pump inhibitor (PPI), which is used for the prevention and treatment of gastric acid-related diseases. A new highly efficient asymmetric oxidation using cumene hydroperoxide (CHP) as the oxidant in the presence of titanium tetraisopropoxide (Ti(OiPr)₄) and (+)-(1R,2S)-cis-1-amino-2-indanol, in a polar aprotic solvent at 0-20 °C, has been developed to prepare tenatoprazole with an enantiomeric excess of >99%, a chemoselectivity of >90% and a chemical yield of >90% from the corresponding sulfide. This procedure was successfully implemented on scales ranging from 100 mg to multiple kilograms. Detailed studies of the parameters controlling purity and yield for this reaction are presented.     

(R)-9-[2-(Hydroxyphosphinylmethoxy)propyl]adenine as the precursor molecule for antivirals

The biological importance and practical significance of phosphonates have been a major driving force for antiviral research in the past two decades. We describe in this Letter the potential of the H-phosphinate derivative (R)-9-[2-(hydroxyphosphinylmethoxy)propyl]adenine as the versatile synthetic intermediate in the preparation of N-alkylphosphonamidate and alkylphosphonate series.     

Total synthesis of (−)-2-epi-lentiginosine by use of chiral 5-hydroxy-1,5-dihydropyrrol-2-one as a building block

We have developed a practical synthesis of the chiral lactam as a new chiral building block for alkaloid synthesis. Lipase-catalyzed kinetic resolution of hydroxylactam 8, followed by isolation-racemization of the chiral acetoxylactam 9 provided the optically pure hydroxylactam 8 in 96.0% yield with >99% ee after five cycles of kinetic resolution-racemization process. Chemical transformation of (S)-hydroxylactam 8 furnished chiral (−)-2-epi-lentiginosine (1) in 20% yield in 10 steps with no loss of enantiomeric excess.     

Diastereoselective synthesis of trisubstituted piperidines: a versatile synthon for elaboration of uncommon poly(aza)heterocyclic structures

Hetero Michael addition on chiral β′-amino-α,β-unsaturated ketone furnished, after some structural modifications, β,β′-diaminoketals. Mannich type reaction of these diamines with an aldehyde led, with a high diastereoselectivity, to trisubstituted piperidines. Starting from a functionalized aldehyde and after subsequent deprotection of the amino group, an intramolecular Michael addition provided octahydro-2H-pyrrolo-[3,4-b]-pyridine, an uncommon framework found in compounds exhibiting biological activity.     

Total synthesis of (-)-brevenal: a streamlined strategy for practical synthesis of polycyclic ethers

We describe a streamlined strategy for the practical synthesis of trans-fused polycyclic ethers and its application to a concise total synthesis of (-)-brevenal, a new pentacyclic polyether natural product with intriguing biological activities. The B-, D-, and E-rings were constructed by TEMPO/PhI(OAc)(2)-mediated oxidative lactonization of the corresponding 1,6-diols, with minimal need for manipulation of oxygen functionalities. The B- and E-ring lactones were appropriately functionalized by Suzuki-Miyaura coupling of lactone-derived enol phosphates and subsequent stereoselective hydroboration. The A-ring was formed by our mixed thioacetalization methodology. The AB- and DE-ring fragments were assembled through Suzuki-Miyaura coupling, and the C-ring was forged in the same manner as that for the A-ring. More than two grams of the pentacyclic polyether core of (-)-brevenal have been synthesized by the synthetic route developed in this study.     

A methodology for the synthesis of highly functionalized 2- and 4-aminoquinoline derivatives

A methodology for the synthesis of 2- and 4-aminoquinoline derivatives, which takes advantage of selective activation of 2- or 4-substituent of 2-methylsulfanyl-3-acyl-1H-quinolin-4-one 1, has been developed. Since a procedure for formation of 3-aminoquinolinones from the 4-quinolinone 1 was described previously, the new methodology comprises a general methodology for the selective syntheses of three isomeric 2-, 3- and 4-aminoquinoline derivatives starting with the common 4-quinolinone 1.     

Enantioselective synthesis of R-(+)-α and S-(−)-α-lipoic acid

An efficient synthesis of α-lipoic acid from the readily available cis-2-butene-1,4-diol employing a Claisen orthoester rearrangement and Sharpless asymmetric dihydroxylation as the key steps, is described.     

Design and synthesis of a potential SH2 domain inhibitor bearing a stereodiversified 1,4-cis-enediol scaffold

Synthesis of a potential Src family SH2 domain inhibitor incorporating a 1,4-cis-enediol scaffold is reported. The synthetic route offers straightforward and highly selective access to the enediol and its associated chiral centers. Key steps include stereocontrolled syn-aldol coupling, amide alkynylation, and asymmetric ketone reduction.