Cyclic Carbamates Research Articles

Stereoselective Iodocyclization of (S)-Allylalanine Derivatives: γ-Lactone vs Cyclic Carbamate Formation

An efficient procedure for highly chemo- and stereoselective cyclization of (S)-allylalanine derivatives is reported (diastereomeric ratios up to 96:4) where the reaction course can be completely controlled by switching from gamma-lactones to cyclic carbamates simply with the proper choice of the amino acid protecting groups. Both processes are stereoconvergent and afford the (S,S)-products in high yields, short reaction times, and mild reaction conditions.

Direct N‐Cyclopropylation of Cyclic Amides and Azoles Employing a Cyclopropylbismuth Reagent.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis and biological evaluation of a small library of nojirimycin-derived bicyclic iminosugars

Novel nojirimycin-derived bicyclic structures, containing cyclic carbamate, urea and guanidine moieties have been synthesised starting from suitably protected α-C-vinylnojirimycin and α-C-allylnojirimycin, respectively, and their biological activity against different glycosidases and as antibacterial agents tested.

Oxazolidin-2-one Ring, a Popular Framework in Synthetic Organic Chemistry: Part 1. The Construction of the Oxazolidin-2-one Ring

The 1,3-oxazolidin-2-one nucleus is a popular heterocycle framework in synthetic organic chemistry, as well as in medicinal chemistry. This paper deals with the huge number of synthetic approaches addressed to the construction of this five-member ring, with a particular care for the mechanistic and stereochemical outcome. The 2-oxo-1,3-oxazolidine ring is a cyclic carbamate skeleton quite rare in natural product chemistry but very popular in the Synthetic Organic Chemistry since the Evans' report (1) in 1981 on the use of enantiomerically pure 4- substituted oxazolidin-2-ones as chiral auxiliaries in asymmetric synthesis. Oxazolidinones have also a large application as protective groups for the 1,2-aminoalcohol system. Finally, the introduction in the pharmaceutical market of Linezolid (2), an oxazolidin-2-one-based antibacterial drug, attracted the interest of the scientists and resulted in the production of several publications.

Direct N-Cyclopropylation of Cyclic Amides and Azoles Employing a Cyclopropylbismuth Reagent

Cyclopropanes are commonly found in medicinal chemistry since they provide unique spatial and electronic features, combined with high metabolic stability in liver microsomes. Although many methods are found in the chemist's arsenal to connect a cyclopropyl group to a carbon atom, none exist that perform the direct transfer of this useful fragment onto the nitrogen of a heterocycle or an amide. Considering the importance of nitrogenated compounds in the pharmaceutical industry, we sought to develop an expedient method to N-cyclopropylate azoles and amides. We report herein the direct cyclopropyl transfer reaction onto cyclic amides, isatins, oxindoles, imides, and carbamates employing a nonpyrophoric cyclopropylbismuth reagent. The reaction is catalyzed by copper acetate and proceeds smoothly in dichloromethane at 50 °C in the presence of pyridine. The N-cyclopropylation reaction can also be applied to the preparation of N-cyclopropyl indoles, benzimidazoles, pyrroles, and pyrazoles.

Aqueous Phosphoric Acid as a Mild Reagent for Deprotection of tert-Butyl Carbamates, Esters, and Ethers

Aqueous phosphoric acid (85 wt %) is an effective, environmentally benign reagent for the deprotection of tert-butyl carbamates, tert-butyl esters, and tert-butyl ethers. The reaction conditions are mild and offer good selectivity in the presence of other acid-sensitive groups, including CBZ carbamates, azetidine, benzyl and methyl esters, TBDMS, and methyl phenyl ethers. The mildness of the reaction is further demonstrated in the synthesis of clarithromycin derivative, in which a tert-butyl ester is removed in the presence of cyclic carbamate, lactone, ketal, acetate ester, and epimerizable methyl ketone functionalities. The reaction preserves the stereochemical integrity of the substrates. The reactions are high yielding, and the workup is convenient.

Gold‐Catalyzed Synthesis of Alkylidene 2‐Oxazolidinones and 1,3‐Oxazin‐2‐ones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Gold-Catalyzed Synthesis of Alkylidene 2-Oxazolidinones and 1,3-Oxazin-2-ones

N-Boc-protected alkynylamines are converted into the corresponding alkylidene 2-oxazolidinones or 2-oxazinones under very mild reaction conditions in the presence of 1-5 mol % of a cationic Au(I) complex. The scope of the reaction is very general, providing the cyclic carbamates in high yield regardless of the substitution at nitrogen and alkyne terminus.

Construction of an Advanced Tetracyclic Intermediate for Total Synthesis of the Marine Alkaloid Sarain A

In work directed toward a total synthesis of the marine alkaloid sarain A (1), the advanced intermediate 54, containing all the key elements and the seven stereogenic centers of sarain A, has been successfully synthesized from bicyclic lactam 4, previously prepared via an intramolecular stereospecific [3 + 2]-azomethine ylide dipolar cycloaddition. Intermediate lactam 4 could be efficiently converted to N-Boc derivative 12. Introduction of a two-carbon fragment into lactam 12 which eventually becomes the C-7',8' syn diol of the "eastern" ring was then achieved by C-acylation of the corresponding enolate with methoxyacetyl chloride followed by a highly stereoselective ketone reduction with Zn(BH4)2 to afford alcohol 16. Intermediate 16 has the incorrect C-7' relative stereochemistry for sarain A, but this problem was conveniently remedied by inverting the C-7' center via an intramolecular Ohfune-type cyclization of the silyl carbamate derived from Boc mesylate 27 to produce the key cyclic carbamate 28. It was then possible to convert acetal 28 to allylsilane 32 followed by cyclization to the alkaloid tricyclic core 33 via an allylsilane/N-sulfonyliminium ion cyclization. Formation of the "western" macrocyclic ring has been successfully addressed using functional group handles at C-3' and N-1' on the tricyclic core via a ring-closing olefin metathesis (RCM) strategy with the second-generation Grubbs ruthenium catalyst to produce intermediate macrolactam 47. A chelation-controlled addition of ethynylmagnesium bromide to advanced aldehyde 51 afforded a single diastereomeric adduct 53 which is tentatively assigned to have the correct C-7',8' syn-diol stereochemistry. This adduct could be rearranged to the conveniently protected amino carbonate 54 which is set up for construction of the remainder of the eastern ring of sarain A.

Selective Catalytic Oxidative Carbonylation of Amino Alcohols to Ureas

[reaction: see text] Amino alcohols undergo W(CO)(6)-catalyzed oxidative carbonylation to the corresponding hydroxyalkylureas without protection of the hydroxyl group. Selected examples of 1,2-, 1,3-, 1,4-, and 1,5-amino alcohols were converted to the ureas in good to excellent yields, with only small amounts of the cyclic carbamates being formed. In contrast, the phosgene derivatives CDI and DMDTC undergo stoichiometric reactions with the amino alcohol substrates to afford ureas and cyclic carbamates with variable selectivity.

Synthesis and Comparative Glycosidase Inhibitory Properties of Reducing Castanospermine Analogues

AbstractThe feasibility of the intramolecular nucleophilic addition of the nitrogen atom in cyclic (thio)carbamates with a pseudo‐C‐nucleoside structure to the masked carbonyl group in aldose precursors in the synthesis of reducing (i.e., 5‐hydroxy)6‐oxaindolizidine frameworks is illustrated by the preparation of the 6‐epi, 7‐epi, 8‐epi and 6,8a‐di‐epi diastereomers of the potent glycosidase inhibitor (+)‐castanospermine. In all cases, the increased anomeric effect caused by the high sp2 character of the pseudoamide‐type nitrogen atom resulted in the pseudoanomeric hydroxy group being anchored in an axial orientation in aqueous solution, as in the aglycons in α‐glycosides. These analogs of the natural alkaloid showed a higher selectivity in the inhibition of α‐glucosidases. Structure/glycosidase inhibitory activity studies indicated that inversion of any hydroxy group resulted in a dramatic decrease in the inhibition potency, confirming the critical importance of a correct hydroxylation profile. In the case of (+)‐8‐epi‐6‐oxacastanospermine derivatives, with a hydroxylation profile with a structural complementarity to that of D‐galactose, a moderate but very selective inhibition of α‐galactosidase was observed, supporting the importance of a defined configuration at pseudoanomeric centres for anomeric specificity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Zeolite-based organic–inorganic hybrid catalysts for phosgene-free and solvent-free synthesis of cyclic carbonates and carbamates at mild conditions utilizing CO 2

As-synthesized zeolite-beta exhibits high catalytic activity for the synthesis of cyclic carbonates and alkyl and aryl carbamates by a phosgene-free route, utilizing the greenhouse effect gas CO 2. The reaction occurs with high yields of the desired products at mild conditions and without using any solvent or cocatalyst. Cyclic carbonates are synthesized by cycloaddition reaction of CO 2 with oxiranes (epichlorohydrin, propene oxide, styrene oxide and n-butene oxide) at 393 K and 6.9 bar. Alkyl and aryl carbamates are synthesized by the reaction of the corresponding amines, CO 2 and n-butyl bromide at 353 K and 3.4 bar. The as-synthesized zeolite-beta containing the encapsulated quaternary ammonium ions is not only reusable in several recycling experiments, but also shows superior activity to that of the corresponding homogeneous, quaternary ammonium halide salt generally used in the commercial synthetic practice. The microporous silica (inorganic) acting in concert with the encapsulated organic component constitutes an efficient, recyclable catalyst for this reaction.

Synthesis of cyclic sulfamoyl carbamates and ureas via ring-closing metathesis

Synthetic routes to a diverse set of cyclic sulfamoyl carbamates and ureas are reported. These routes utilize 3-component coupling, Mitsunobu alkylation, and ring-closing metathesis using the second-generation Grubbs catalyst to achieve the synthesis of the target S-heterocyclic compounds. Cyclic S-heterocycles ranging from 9- to 11-membered rings have been obtained.

Silver‐Catalyzed Hydroamination: Synthesis of N‐Bridgehead Pyrroles, Incorporating a Protection‐Deprotection Strategy for Preparation of Cyclic Secondary Vinylogous Carbamates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Efficient and Selective Deprotection Method for N‐Protected 2(3H)‐Benzoxazolones and 2(3H)‐Benzothiazolones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Silver‐Catalyzed Hydroamination: Synthesis of N‐Bridgehead Pyrroles, Incorporating a Protection‐Deprotection Strategy for Preparation of Cyclic Secondary Vinylogous Carbamates

AbstractN‐Bridgehead pyrroles are efficiently prepared from cyclic secondary vinylogous carbamates using a two‐step sequence. This sequence involves C‐propargylation followed by a silver‐catalyzed intramolecular hydroamination. Hydroamination is brought about using microwave irradiation and affords the desired N‐bridgehead pyrroles rapidly and in good yield. Cyclic secondary vinylogous carbamates are prepared using a mild, economical procedure. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

A new approach to vinyl glycine derivatives from (+)-( RS)-3-[( p-toluenesulfinyl)methyl]-1-oxa-4-azaspiro[4,5]decen-3-ene

The diastereoselective reduction of α-benzyl-α-sulfinylketimine 1a with DIBAL–H/ZnCl 2, LiEt 3BH, and NaCNBH 3/AcOH–TFA has been studied. Under the first conditions, the reaction was completely stereoselective and the sulfinyl group involving the formation of a chelated complex with the metallic ion became the sole chiral controller, regardless of the presence of the α-stereocentre. The title compound 6-I was derivatized as cyclic carbamate 2 and the base induced desulfinylation of this compound allowed the synthesis of the enantiomerically pure N, O-protected N-cyclohexyl-1,2-amino alcohol 3 with total regio- and stereocontrol.

Efficient and selective deprotection method for N-protected 2( 3H)-benzoxazolones and 2( 3H)-benzothiazolones

Cyclic carbamate flanked with heterocyclic or aliphatic moieties are frequently used in medicinal chemistry. The synthesis of derivatives bearing a free NH often requires the use of a protection method. A literature search reveals very few protection/deprotection methods for cyclic carbamates. In this paper, we described different methods applicable to 2( 3H)-benzoxazolone and 2( 3H)-benzothiazolone.

A New Synthetic Method of 1,4‐Dihydro‐2H‐3,1‐benzoxazin‐2‐ones: Selenium‐Catalyzed Reductive Carbonylation of Aromatic Nitro Compounds with Carbon Monoxide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Novel ketolide antibiotics with a fused five-membered lactone ring––synthesis, physicochemical and antimicrobial properties

In an effort to find novel semisynthetic macrolides with extended antibacterial spectrum and improved activity we prepared a series of compounds based on commercially available clarithromycin, a potent and safe antimicrobial agent of outstanding clinical and commercial interest. According to the literature, improvement of antibacterial activity of erythromycin type antibiotics can be achieved by introduction of fused heterocycles such as cyclic carbonates or carbamates at positions 11 and 12 (such as in telithromycin). In the course of the work presented here, a similar, hitherto unprecedented set of compounds bearing a five-membered lactone ring fused to positions 11 and 12 was prepared based on carbon–carbon bond formation via intramolecular Michael addition of a [(hetero)arylalkylthio]acetic acid ester enolate to an α,β-unsaturated ketone as the key step. Some of the ketolide compounds described in this paper were highly active against a representative set of erythromycin sensitive and erythromycin resistant test strains. The best compound showed a similar antimicrobial spectrum and comparable activity in vitro as well as in vivo as telithromycin. Furthermore, some physicochemical properties of these compounds were determined and are presented here. On the basis of these results, the novel ketolide lactones presented in this paper emerged as valuable lead compounds with comparable properties as the commercial ketolide antibacterial telithromycin (Ketek TM).