An asymmetric synthesis of (+)-grandisol, a constituent of the aggregation pheromone of the cotton boll weevil, via a kinetic resolution

A novel approach to the asymmetric synthesis of (+)-grandisol, (1R, 2S)-isopropenyl-1-methylcyclobutaneethanol, involves the use of catalytic kinetic resolution of a primary allylic alcohol, [(1RS, 5SR)-5-methylbicyclo[3.2.0]hept-2-en-2-yl] methanol. The allylic alcohol is prepared in four steps from simple achiral materials involving the use of a modified Shapiro reaction. The resolved alcohol (95% ee) is then reduced in two steps to the corresponding methyl alkene, (1S,5R)-2,5-dimethylbicyclo[3.2.0]hept-2-ene. This alkene is converted to (+)-grandisol (95% ee), in three steps, by modified literature procedures.     

Facile synthesis of suvorexant,an orexin receptor antagonist,via a chiral diazepane intermediate

A facile synthesis of suvorexant,an orexin receptor antagonist,is described.The key intermediate 6 was prepared from R-3-aminobutyric acid through protection,condensation,deprotection,cyclization,and hydrogenation steps.The title product was obtained with a total yield of 31%(>99%ee) after eight linear steps using commercially available raw materials.     

A short enantioselective synthesis of guggultetrol,a naturally occurring lipid

An enantioselective synthesis of the naturally occurring lipid, guggultetrol, is described with an overall yield of 24% starting from commercially available l-pentadecanol in ten linear steps. The key chiral-inducing steps include a Sharpless asymmetric epoxidation of allylic alcohol and a dihydroxylation of an α,β-unsaturated ester.     

Total synthesis of landomycin A, a potent antitumor angucycline antibiotic

The first total synthesis of landomycin A, the longest and most potent antitumor angucycline antibiotic, has been achieved in 63 steps and 0.34% overall yield starting from 2,5-dihydroxybenzoic acid, 3,5-dimethylphenol, triacetyl d-glucal, and d-xylose, with a convergent linear sequence of 21 steps.     

Total synthesis of lobatoside E, a potent antitumor cyclic triterpene saponin

Lobatoside E, a novel and complex cyclic triterpene saponin showing potent antitumor activities, has been synthesized for the first time, employing a highly modular approach. The synthesis, starting with oleanolic acid, D-glucose, D-galactose, L-arabinose, and L-rhamnose, requires a total of 73 steps, with the longest linear sequence of 31 steps and in 1.2% overall yield.     

Synthesis of protected （2S,4R）-2-amino-4-methyldecanoic acid,a proposed component of culicinins

The protected （2S,4R）-2-amino-4-methyldecanoic acid, a proposed component of culicinins has been synthesized over 10 steps and in total 28% yields using Wittig reaction and Schollkopf amino acid synthesis as key steps.     

Total synthesis of thapsigargin, a potent SERCA pump inhibitor

The enantioselective total synthesis of thapsigargin, a potent, selective inhibitor of the Ca2+ pump SERCA, is described. Starting from ketoalcohol 8, key steps involve regioselective introduction of the internal olefin at C4-C5, judicious protecting group choice to allow chelation-controlled reduction at C3, and chemoselective introduction of the angelate ester function at C3-O. A selective esterification approach completes the total synthesis in a total of 42 steps and 0.61% overall yield (88.6% average yield per step). [reaction: see text].     

Asymmetric synthesis of isohaliclorensin,a key intermediate of bisquinolinylpyrrole alkaloid halitulin

A new enantioselective total synthesis of N-(3′-aminopropyl)-3-methylazacyclodecane, a partial structure of halitulin, has been achieved in eight steps with 14% overall yield. The key steps are the photochemical ring-expansion reaction of spirooxaziridine to lactam for constructing the azacyclodecane moiety and 1,4-stereoinductive methylation of the resulting lactam.     

Efficient synthesis of novel pentacyclic 6,7-dihydro-5a,7a,13,14-tetraaza-pentaphene-5,8-diones

The convenient synthesis of novel tetraaza-pentaphene-5,8-diones (3) is described, in two steps, from anthranilic acid derivatives, via a microwave-assisted Niementowski reaction. A short evaluation of the antiproliferative activity of these new pentacyclic heterocycles was realised.     

Synthesis of Isobrassilexin,a Biologically Active Isomer of Brassilexin,a Cruciferac Phytoalexin

The synthesis of isobrassilexin 2, a hitherto non natural indoloisothiazole is reported (two steps, 43% yield). This substance, an isomer of brassilexin 1 has shown important biological properties in vitro.     

Syntheses of strychnine, norfluorocurarine, dehydrodesacetylretuline, and valparicine enabled by intramolecular cycloadditions of Zincke aldehydes

A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions of tryptamine-derived Zincke aldehydes is described. This important complexity-generating transformation provides the tetracyclic core of many indole monoterpene alkaloids in only three steps from commercially available starting materials and played a key role in short syntheses of norfluorocurarine (five steps), dehydrodesacetylretuline (six steps), valparicine (seven steps), and strychnine (six steps). Reasonable mechanistic possibilities for this reaction, a surprisingly facile dimerization of the products, and an unexpected cycloreversion to regenerate Zincke aldehydes under specific conditions are also discussed.     

Syntheses of potential metabolites of a potent kappa-opioid receptor agonist, TRK-820

Chemical syntheses of three kinds of potential metabolites of TRK-820, a potent kappa-opioid receptor agonist, were described. One of the potential metabolites 2, 17-N-dealkylated TRK-820, was synthesized starting from noroxycodone through 8 steps in 21% total yield. Glucuronidation of intermediate 10 and compound 1, the free base of TRK-820, was carried out stereoselectively to give 3-O-beta-D-glucuronides 15 and 16 in good yields, respectively. Syntheses of potential conjugated metabolites 3 and 4 were accomplished through 10 steps and 2 steps in 11% and 43% total yields, respectively. Among the potential metabolites of TRK-820, compounds 2 and 4 were identified as metabolites in human hepatocytes. The results of pharmacological studies of compounds 2, 3, and 4 are described.     

Synthesis of a caryophyllene isoprenologue, a potential diterpene natural product

(−)-β-Caryophyllene has been converted into three stereoisomers of a new bicyclic compound that is structurally related to the known macrocyclic diterpene, flexibilene, in the same way β-caryophyllene is related to humulene. Key steps are selective cleavage of caryophyllene, addition of a five carbon component by a Wittig reaction and McMurry cyclization.     

Efficient Total Synthesis of (S)-Dihydroresorcylide, a Bioactive Twelve-Membered Macrolide

The efficient synthesis of (S)‐dihydroresorcylide ( 1a ) along with trans‐resorcylide dimethyl ether ( 2b ), was achieved in linear 9 steps from commercially available orcinol monohydrate ( 6 ) with esterification, carbonylation, and ring‐closing metathesis (RCM) as the key steps in the synthetic sequence.     

Synthesis of betavulgaroside III, a representative triterpene seco-glycoside

Triterpene seco-glycosides constitute a small family of the plant saponins which feature a terminal seco-saccharide appendage deriving supposedly from oxidative scission of a monosaccharide unit. Herein, we have developed synthetic approaches for the first time to the access to these molecules. Betavulgaroside III (1), a representative congener occurring in Beta vulgaris and Achyranthes fauriei, is successfully synthesized in a total of 31 steps with L-arabinose, D-glucose, and oleanolic acid as starting materials. The longest linear sequence requires 23 steps and in an overall 0.9% yield (from D-glucose). The synthesis features oxidative elaboration of the seco-saccharide unit prior to assembly of the triterpene 3,28-bisglycoside. This tactic has been proven superior, in the attempts to the synthesis of the more easily accessible 2'-epi-betavulgaroside III (2), to that employing oxidative cleavage of the terminal saccharide unit at an advanced triterpene 3,28-bisglycoside scaffold.     

A simple, efficient, and enantiocontrolled synthesis of a near-structural mimic of platensimycin

A close structural relative of platensimycin was synthesized efficiently in nine steps.     

Total synthesis of lamellarins D, H, and R and ningalin B

A concise total synthesis of lamellarins D (7 steps), H (7 steps), and R (5 steps) and ningalin B (5 steps) is achieved starting from the corresponding aldehydes and amines. The synthesis features three oxidative reactions as key steps in a biomimetic manner, involving an AgOAc-mediated oxidative coupling reaction to construct the pyrrole core, a Pb(OAc)(4)-induced oxidative cyclization to form the lactone, and Kita's oxidation reaction to form the pyrrole-arene C-C bond.     

一叶秋碱全合成的研究-中间体α-羟酮的合成

α-羟酮是中枢神经药物叶 碱 合中的重要中间体。本文以不同路线合成了α羟酮, 并通过与天然降解物进行光谱对照确定了结构。     

Facile synthesis of monoacetylated spermidines, illustrating selective deacetylation and application of a common precursor

The synthesis of all three monoacetylated spermidines is reported. N4-Acetylspermidine was obtained in four steps from spermidine via the triacetylated intermediate by selective deacetylation after exhaustive t-butoxycarbonylation as well as directly from a previously described protected precursor. N1-Acetylspermidine and N8-acetylspermidine were both obtained in four simple protection/deprotection steps from a common, selectively protected compound, thus illustrating the versatility of the latter.     

Enantioselective total synthesis of (-)-acetylaranotin, a dihydrooxepine epidithiodiketopiperazine

The first total synthesis of the dihydrooxepine-containing epidithiodiketopiperazine (ETP) (-)-acetylaranotin (1) is reported. The key steps of the synthesis include an enantioselective azomethine ylide (1,3)-dipolar cycloaddition reaction to set the absolute and relative stereochemistry, a rhodium-catalyzed cycloisomerization/chloride elimination sequence to generate the dihydrooxepine moiety, and a stereoretentive diketopiperazine sulfenylation to install the epidisulfide. This synthesis provides access to (-)-1 in 18 steps from inexpensive, commercially available starting materials. We anticipate that the approach described herein will serve as a general strategy for the synthesis of additional members of the dihydrooxepine ETP family.