A concise synthesis of (−)-cytoxazone and (−)-4-epi-cytoxazone using chlorosulfonyl isocyanate

A concise synthesis of (−)-cytoxazone and its stereoisomer (−)-4-epi-cytoxazone, novel cytokine modulators, has been accomplished each in six steps from readily available p-anisaldehyde with good diastereoselectivity. Key steps in the synthesis include the regioselective and diastereoselective amination of anti- and syn-1,2-dimethyl ethers with chlorosulfonyl isocyanate and the subsequent regioselective cyclization of the diol to construct the oxazolidin-2-one core. The diastereoselectivity of amination reaction using CSI was explained by the Cieplak electronic model via S_N1 mechanism and neighboring group effect, leading to the retention of the configuration.     

Novel synthetic method for allylic amination of cyclic allylic ethers using chlorosulfonyl isocyanate

The introduction of amines to allylic or benzylic position of cyclic compounds with chlorosulfonyl isocyanate is developed in high to excellent yields. This method provides a novel access to biologically active compounds including the framework of 1-aminoindanes, 1-aminotetralines, and 1-amino-2-hydroxy cyclic compounds. Mechanistic evidence for the reaction pathway is also provided.     

An efficient stereoselective synthesis of (2S,3S)-3-hydroxypipecolic acid using chlorosulfonyl isocyanate

An efficient stereoselective syntheses of (2S,3S)-3-hydroxypipecolic acid and (2R,3S)-2-hydroxymethylpiperidin-3-ol were achieved from p-anisaldehyde via the regioselective and diastereoselective introduction of an N-protected amine group using chlorosulfonyl isocyanate, ring-closing methathesis, and oxidation of p-methoxyphenyl group as the key steps.     

Asymmetric total synthesis of (S)-dapoxetine

A concise asymmetric total synthesis of (S)-dapoxetine from commercially available 3-chloropropiophenone is described. The key step includes a highly stereoselective amination of chiral benzylic ether, with the retention of stereochemistry, using chlorosulfonyl isocyanate.     

One-pot synthesis of N-acyl-substituted sulfamides from chlorosulfonyl isocyanate via the Burgess-type intermediates

The title N-alkoxycarbonyl- or N-aryloxycarbonyl-substituted sulfamides were synthesised in one-pot in efficient yields from chlorosulfonyl isocyanate (CSI), alcohols and aqueous (or dry) amines via the corresponding water-resistant intermediates, carboxysulfamoylammonium salts (Burgess-type reagents), which were generated in situ by the deactivation of the corresponding water-sensitive N-(chlorosulfonyl)carbamates with tertiary amines.     

Regioselective and diastereoselective amination of polybenzyl ethers using chlorosulfonyl isocyanate: total syntheses of 1,4-dideoxy-1,4-imino-D-arabinitol and (-)-lentiginosine

The total syntheses of DAB1 (1) and (-)-lentiginosine (2) were concisely accomplished from D-lyxose via regioselective and diastereoselective NHCbz introduction using CSI, chemoselective removal of the Cbz protection, and ring-closing metathesis as key steps.     

Stereoselective synthesis of (−)-cytoxazone and (+)-epi-cytoxazone

Optically pure (−)-cytoxazone was synthesized, starting from methyl p-methoxycinnamate, in six steps and in 31% overall yield. The required anti-aminoalcohol configuration was established by combining Sharpless asymmetric aminohydroxylation with the configurational inversion of the intermediate amidoalcohol via an oxazoline. The synthesis of (+)-epi-cytoxazone is also described.     

Regioselective and diastereoselective allylic amination using chlorosulfonyl isocyanate. A novel asymmetric synthesis of unsaturated aromatic 1,2-amino alcohols

The diastereoselective synthesis of unsaturated aromatic 1,2-amino alcohols can be achieved on an epimeric mixture of optically active allylic ethers having a hydroxyl group attached to an allylic chiral center to the pi-system using chlorosulfonyl isocyanate. These reactions produced the unsaturated anti-1,2-amino alcohols either exclusively or predominantly only for aromatic derivatives. The anti-selectivity may be explained by the Cieplak electronic model during the conversion from ethers to carbamates.     

Enantioselective synthesis of (−)-cytoxazone and (+)-epi-cytoxazone via Rh-catalyzed diastereoselective oxidative C-H aminations

An efficient enantioselective synthesis of (−)-cytoxazone (1) and (+)-epi-cytoxazone (2) using proline-catalyzed asymmetric α-amino-oxylation of aldehydes followed by Rh-catalyzed diastereoselective oxidative C-H amination as the key steps is described. syn or anti 1,2-aminoalcohols were obtained by Rh-catalyzed intramolecular amidation of the C-H bonds of carbamates or sulfamate esters with good to excellent diastereoselectivity.     

Regioselective and diastereoselective amination with use of chlorosulfonyl isocyanate: a short and efficient synthesis of (-)-cytoxazone

The total synthesis of (-)-cytoxazone 1 was achieved in six linear steps (34% overall yield) from p-anisaldehyde. The key steps in this route are the regioselective and stereoselective introduction of a N-protected amine group, using the CSI reaction of the anti-1,2-dimethyl ether 3, and the subsequent regioselective cyclization of the N-protected amino diol 13 to give the 2-oxazolidinone unit of (-)-cytoxazone 1. [reaction: see text]     

Total synthesis of (−)-codonopsinol and (+)-2-epi codonopsinol via acid catalyzed amido cyclisation

A short and stereoselective synthesis of (−)-codonopsinol 5 and its C-2 epimer 6 were accomplished from commercially available starting material d-1,5-gluconolactone, using acid mediated amido cyclisation as the key step. The inhibitory activitiy of these compounds against glucosidase and galactosidase has been studied.     

Total synthesis of (−)-diospongin A and (+)-cryptofolione via asymmetric aldol reaction

Stereoselective synthesis of two distinctive pyranone skeletons diospongin A and cryptofolione has been described based on an asymmetric aldol reaction starting from Chan’s diene. The synthetic strategy involves the enantioselective Mukaiyama aldol, diastereoselective reduction of δ-hydroxy-β-keto ester, a tandem sequence of deprotection, and intramolecular oxa-Michael reaction to obtain diospongin A and an asymmetric allylation and lactone formation using ring-closing metathesis reaction to obtain cryptofolione.     

A short enantioselective synthesis of (−)-chloramphenicol and (+)-thiamphenicol using tethered aminohydroxylation

An efficient enantioselective synthesis of (−)-chloramphenicol (1) and (+)-thiamphenicol (2) is described. These antibiotics have been synthesized from commercially available 4-nitrobenzaldehyde and 4-(methylthio)benzaldehyde, respectively, using tethered aminohydroxylation and Sharpless asymmetric epoxidation as the chirality inducing steps.     

A concise diastereoselective approach to (+)-dexoxadrol, (−)-epi-dexoxadrol, (−)-conhydrine and (+)-lentiginosine from (−)-pipecolinic acid

A new diastereoselective pathway for the total synthesis of (+)-dexoxadrol, first asymmetric synthesis of (−)-epi-dexoxadrol and formal synthesis of conhydrine and (+)-lentiginosine is presented using commercially available (−)-pipecolinic acid. The key reactions utilized are Sharpless asymmetric dihydroxylation and Wittig reaction. The paper further describes the study of effect of protecting groups on dihydroxylation of a terminal olefin in piperidine ring system.     

Stereospecific total synthesis of (−)-8-epi-hyperaspine

Condensation of protected δ-hydroxy-β-amino ester 7 with a β-keto ester provides vinylogous urethane 8, which is cyclized under the action of t-BuOK followed by decarboxylation to afford enone 12. Hydrogenation of 12 or its N,O-diprotected derivative 13 gives 2,6-cis-disubstituted piperdines. Using these intermediates, (−)-8-epi-hyperaspine is synthesized.     

Syntheses of (−)-gabosine A, (+)-4-epi-gabosine A, (−)-gabosine E, and (+)-4-epi-gabosine E

(+)-4-epi-Gabosine A 1 and (−)-gabosine A 2 have been synthesized starting from methyl α,d-glucopyranoside and methyl α,d-mannopyranoside, respectively, by utilizing Pd(0) catalyzed Stille coupling as the key step. On the other hand, syntheses of (+)-4-epi-gabosine E 3 and (−)-gabosine E 4 have been accomplished from methyl α,d-glucopyranoside and from methyl α,d-mannopyranoside, respectively, by utilizing DMAP catalyzed Morita-Baylis-Hillman reaction as the key step. Presence of acetyl group at C-6 position of sugar derived cyclic enone prevented the aromatization of MBH adduct. A plausible mechanism is also described.     

Ir-catalyzed asymmetric allylic alkylation using chiral diaminophosphine oxides: DIAPHOXs. Formal enantioselective synthesis of (−)-paroxetine

An Ir-catalyzed asymmetric allylic alkylation using chiral diaminophosphine oxide is described. Asymmetric allylic alkylation of terminal allylic carbonates proceeded using 5 mol % of Ir catalyst, 5 mol % of DIAPHOX 1i, 10 mol % of NaPF₆, 10 mol % of LiOAc, and N,O-bis(trimethylsilyl)acetamide (BSA), affording the corresponding branched products in excellent yield and in up to 95% ee. The developed catalytic asymmetric reaction was successfully applied to a formal enantioselective synthesis of (−)-paroxetine.     

Enantioselective synthesis of (−)-cytoxazone and (+)-epi-cytoxazone, novel cytokine modulators via Sharpless asymmetric epoxidation and l-proline catalyzed Mannich reaction

A short and efficient enantioselective synthesis of (−)-cytoxazone and its stereoisomer (+)-epi-cytoxazone, novel cytokine modulators, has been described with good yield and enantioselectivity. Ti-catalyzed Sharpless asymmetric epoxidation of allyl alcohol and l-proline catalyzed three-component Mannich reaction constitute the key steps in introducing stereogenicity into the molecule.     

Organocatalytic enantioselective synthesis of quinolizidine alkaloids (+)-myrtine, (−)-lupinine, and (+)-epiepiquinamide

The organocatalytic synthesis of quinolizidine alkaloids (+)-myrtine, (−)-lupinine, and (+)-epiepiquinamide is described. It involved, as the key step, an enantioselective intramolecular aza-Michael reaction (IMAMR) catalyzed by Jørgensen catalyst I, affording the common precursor with high enantioselectivity. This compound was subsequently transformed into the three alkaloids in a highly diastereoselective manner.     

New asymmetric strategy for the total synthesis of naturally occurring (+)-alexine and (−)-7-epi-alexine

A novel and highly convenient process is described for the asymmetric synthesis of polyhydroxylated pyrrolizidine alkaloids, (+)-alexine [(1R,2R,3R,7S,7aS)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine] and (−)-7-epi-alexine [(1R,2R,3R,7R,7aS)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine], as the potent glycosidase inhibitors by featuring the efficient and stereodefined elaboration of the functionalized pyrrolidine derivatives, which were, in turn, prepared via stereoselective manipulation of the homochiral allyl alcohol precursors derived from l-xylose.