Modifications at the 6-O-position of 1-deoxynojirimycin: facile and efficient synthesis of 6-O-alkylated-N-octyl-1-deoxynojirimycin derivatives

A straightforward synthesis of N-alkylated 1-deoxynojirimycin derivatives modified at the 6-O-position has been described. The key intermediate in the synthesis of target compounds was 2,3,4-tri-O-benzyl-1,5-dideoxy-1,5-imino-D-glucitol, which was prepared from 2,3,4,6-tetra-O-benzyl-1,5-dideoxy-1,5-imino-D-glucitol. Optimal conditions have been established for the synthesis of the key intermediate by varying reaction parameters. Reductive amination and subsequent alkylation of the 6-O-position followed by hydrogenolysis were the main reaction steps, which gave target compounds 6-O-ethyl-N-octyl-1,5-dideoxy-1,5-imino-D-glucitol and 6-O-butyl-N-octyl-1,5-dideoxy-1,5-imino-D-glucitol. This synthetic route is flexible and can be useful for the synthesis of other lipophilic iminosugar derivatives.     

Notiz zur Synthese von rac. cis- und trans-2-Nor-abscisinsäure

Note on the synthesis of rac. cis- and trans-nor-abscisic acid The synthesis of the 2-nor-analogues of cis- and trans-abscicic acid is described.     

Intramolecular Wittig Reaction: A New Synthesis of (S)‐Pyrrolam A

A straightforward synthesis of (S)‐pyrrolam A is described. The synthesis involves in situ generation of the phosphorane 3 , followed by an intramolecular Wittig reaction to furnish (S)‐pyrrolam A.     

Total Synthesis of (+)-Lactacystin

A double stereodifferentiating crotylation between aldehyde 1 and silane (S)- 2 to afford homoallylic alcohol 3 is the key diastereoselective step (anti:syn >30:1) in an efficient asymmetric synthesis of (+)-lactacystin. This compound is a metabolite isolated from Streptomyces sp. OM-6519 that exhibits significant neurotrophic activity. An additional important step in the synthesis is a catalytic asymmetric aminohydroxylation used as the key step in the synthesis of the (2R,3S)-hydroxyleucine synthon.     

Chemistry of the phenoxathiins. III. Synthesis of benzo[1″,2″:5,6:5″,4″:5′,6′]bis[1,4]oxathiino[3,2-b:3′,2′-b']dipyridine

As a result of studies dealing with the synthesis of 1-azaphenoxathiins, the synthesis of benzo[1″,2″:5,6:5″,4″:5′,6′]bis[1,4]oxathiino[3,2-b:3′,2′-b']dipyridine was examined. Unique evidence of solvent participation in the synthesis of these compounds by the structure elucidation of a novel minor by-product formed during the synthesis of the title compound is also reported.     

Microwave-Assisted Synthesis of Six-Membered O-Heterocycles

The development of new strategies for synthesis of six-membered O-heterocycles has remained a highly attractive but challenging proposition. An overview of the application of microwave irradiation in oxygen-containing six-membered heterocyclic compounds synthesis is presented, focusing on the developments in the past 5–10 years. This contribution covers the literature concerning the total synthesis of six membered O-heterocycles.     

Synthesis of Enantiomerically Pure Isoxazolidine Monomers for the Preparation of β3‐Oligopeptides by Iterative α‐Keto Acid?Hydroxylamine (KAHA) Ligations

A versatile method for the synthesis of enantiomerically pure isoxazolidine monomers for the synthesis of β³‐oligopeptides via α‐keto acid? hydroxylamine (KAHA) ligation is presented. This one‐pot synthetic method utilizes in situ generated nitrones bearing gulose‐derived chiral auxiliaries for the asymmetric 1,3‐dipolar cycloaddition with methyl 2‐methoxyacrylate. The resulting enantiomerically pure isoxazolidine monomers bearing diverse side chains (proteinogenic and non‐proteinogenic) can be synthesized in either configuration (like‐ and unlike‐configured). The scalable and enantioselective synthesis of the isoxazolidine monomers enables the use of the synthesis of β³‐oligopeptides via iterative α‐keto acid? hydroxylamine (KAHA) ligation.     

Synthesis of dimethyl heterocyclic‐o‐dicarboxylates using dimethyl acetylenedicarboxylate

Dimethyl acetylenedicarboxylate (DMAD) is a very important and useful reagent for the preparation of dimethyl heterocyclic‐o‐dicarboxylates, which are key intermediates in the synthesis of fused pyridazine derivatives. The synthesis of thiopyranes by the Diels‐Alder reaction of dithiocarboxylate derivatives, synthesis of various cyclazines by [2 + 8] cycloaddition reactions, and synthesis of dimethyl pyrazolo[3,4‐b]pyridine‐5,6‐dicarboxylates and polycyclic heterocycles containing the 1,6‐naphthyridine ring system by the reaction of o‐aminonitrile compounds with DMAD are described here.     

A Total Synthesis of Aliskiren

A total synthesis of aliskiren ( 20 ) was accomplished. A key in our synthesis was to use the symmetric trans‐cisoid‐trans‐bis‐lactone 1 as a precursor. It was expediently prepared by three different routes (Scheme 2). Appending the end groups and functional group transformations completed the synthesis (Scheme 3).     

Modular Synthesis of Nona-Decasaccharide Motif from Psidium guajava Polysaccharides: Orthogonal One-Pot Glycosylation Strategy

The synthesis of long, branched, and complex carbohydrate sequences remains a challenging task in chemical synthesis. Reported here is an efficient and modular one-pot synthesis of a nona-decasaccharide and shorter sequences from Psidium guajava polysaccharides, which have the potent α-glucosidase inhibitory activity. The synthetic strategy features: 1) several one-pot glycosylation reactions on the basis of N-phenyltrifluoroacetimidate (PTFAI) and Yu glycosylation to streamline the chemical synthesis of oligosaccharides, 2) the successful and efficient assembly sequences (first O3′, second O5′, final O2′) toward the challenging 2,3,5-branched Araf motif, 3) the stereoselective 1,2-cis-glucosylation by reagent control, and 4) the convergent [6+6+7] one-pot coupling reaction for the final assembly of the target nona-decasaccharide. This orthogonal one-pot glycosylation strategy can streamline the chemical synthesis of long, branched, and complicated carbohydrate chains.     

Microwave-Assisted Synthesis of Six-Membered S-Heterocycles

The development of new strategies for synthesis of six-membered S-heterocycles has remained a highly attractive but challenging proposition. An overview of the application of microwave irradiation in sulfur-containing six-membered heterocyclic compounds synthesis is presented, focusing on the developments in the past 5–10 years. This contribution covers the literature concerning the total synthesis of six-membered S-heterocycles.     

Asymmetric synthesis of machilin C and its analogue

Full details of the asymmetric total synthesis of erythro-8-O-4′-neolignan, machilin C, and its analogue perseal A are reported. The synthesis was involved in the Sharpless dihydroxylation reaction that occurred with excellent asymmetric induction, and the Mitsunobu reaction which occurred with inversion of the absolute configuration from the threo to the erythro isomer. The synthesis was achieved from simple vanillin in eight to twelve steps.     

Synthesis and pharmacological activities of some dibenzopyrazolocinnolines and dibenzopyridazinoquinoxalines

Derivatives of three new classes of heterocyclic compounds have been synthesized. The first class comprises the synthesis of pyrimidino- and imidazolopyrazolopyridazine using 11 H-dibenzo[f,h]pyrazolo[3,4-c]-cinnoline-13-amine. The second class involves the synthesis of triazine derivatives using 11 H-dibenzo-[f,h]pyrazolo[3,4-c]cinnoline-13-diazonium chloride. The third class deals with the synthesis of polycyclic compounds using dibenzo[f,h]pyridazino[4,5-b]quinoxaline-10,13-diamine. The pharmacological screening has shown that several of these compounds have good antiparkinsonian activities comparable to Benzatropine. The detailed synthesis, spectroscopic data, and pharmacological properties are reported.     

Preparative solid state chemistry. Recent developments

A survey of recent developments in preparative solid state chemistry shows that, with a knowledge of structural chemistry and reactivity patterns of solids, it is possible to synthesize a variety of new solids possessing novel structures. A distinction is made between synthesis ofnew solids and synthesis of solids bynew methods. Three new routes to solid state synthesis are recognized: the precursor method, and topochemical methods involving redox and ion-exchange reactions. The low-temperature topochemical methods enable synthesis of metastable phases that are inaccessible by the high temperature route. Several illustrative examples of solid state synthesis from the recent literature are presented.     

Fawcettimine‐Type Lycopodium Alkaloids as a Driving Force for Discoveries in Organic Synthesis

Ever since the pioneering synthetic work reported by both Inubushi and Heathcock back in 1980s, the fawcettimine‐type Lycopodium alkaloids have continuously served as a driving force for discoveries in organic synthesis. In this personal account, we summarized our recent synthetic efforts towards the total synthesis of fawcettimine‐type Lycopodium alkaloids, along with a brief summary of relevant syntheses reported by others. Our discussions focus mainly on the key reactions applied during the synthesis of fawcettimine‐type Lycopodium alkaloids.     

Modular Synthesis of Nona‐Decasaccharide Motif from Psidium guajava Polysaccharides: Orthogonal One‐Pot Glycosylation Strategy

The synthesis of long, branched, and complex carbohydrate sequences remains a challenging task in chemical synthesis. Reported here is an efficient and modular one‐pot synthesis of a nona‐decasaccharide and shorter sequences from Psidium guajava polysaccharides, which have the potent α‐glucosidase inhibitory activity. The synthetic strategy features: 1) several one‐pot glycosylation reactions on the basis of N‐phenyltrifluoroacetimidate (PTFAI) and Yu glycosylation to streamline the chemical synthesis of oligosaccharides, 2) the successful and efficient assembly sequences (first O3′, second O5′, final O2′) toward the challenging 2,3,5‐branched Araf motif, 3) the stereoselective 1,2‐cis‐glucosylation by reagent control, and 4) the convergent [6+6+7] one‐pot coupling reaction for the final assembly of the target nona‐decasaccharide. This orthogonal one‐pot glycosylation strategy can streamline the chemical synthesis of long, branched, and complicated carbohydrate chains.     

A Stereoselective Total Synthesis of Xyolide,a Natural Bioactive Nonenolide

A stereoselective total synthesis of xyolide, a naturally occurring bioactive nonenolide, has been accomplished. The acid fragment of the molecule has been prepared from D ‐mannitol and the alcohol fragment from (2Z)‐but‐2‐ene‐1,4‐diol. The synthesis involves the coupling of these two fragments using the Yamaguchi esterification protocol, followed by intramolecular ring‐closing methathesis. The diastereoisomeric alcohol fragment has also been utilized in this synthesis by employing the Mitsunobu esterification.     

Synthesis of O‐Acyl Isopeptides

O‐Acyl isopeptides, in which the N‐acyl linkage on the hydroxyamino acid residue (e.g., Ser and Thr) is replaced with an O‐acyl linkage, generally possess superior water‐solubility to their corresponding native peptides, as well as other distinct physicochemical properties. In addition, O‐acyl isopeptides can be rapidly converted into their corresponding native peptide under neutral aqueous conditions through an O‐to‐N acyl migration. By exploiting these characteristics, researchers have applied the O‐acyl isopeptide method to various peptide‐synthesis fields, such as the synthesis of aggregative peptides and convergent peptide synthesis. This O‐acyl‐isopeptide approach also serves as a means to control the biological function of the peptide in question. Herein, we report the synthesis of O‐acyl isopeptides and some of their applications.     

Directed Metalation?Cross‐Coupling Strategies. Total Syntheses of the Alleged and the Revised Phenanthrene Natural Product Gymnopusin

The total synthesis of gymnopusin ( 2 ) is described. The originally assigned structure for gymnopusin 1a was found to be incorrect by total synthesis using the Directed ortho‐Metalation (DoM)? Cross‐Coupling? Directed remote Metalation (DreM) sequence, a demonstrable key strategy for the regioselective construction of the 9‐phenanthrol core. The revised structure of gymnopusin ( 2 ) was confirmed by synthesis by adopting the same strategy but involving a key remote anionic Fries‐rearrangement step. Both routes highlight methodologies and concepts which may be of value in the regiocontrolled synthesis of phenanthrenoids specifically and in complex polycyclic aromatics in general.     

Microwave-Assisted Synthesis of Five-Membered O-Heterocycles

The development of new strategies for synthesis of five-membered O-heterocycles has remained a highly attractive but challenging proposition. An overview of the application of microwave irradiation in oxygen-containing five-membered heterocyclic compound synthesis is presented, focusing on the developments in the past 5–10 years. This contribution covers the literature concerning the total synthesis of five-membered O-heterocycles.