Synthesis of the bis-spiroacetal moiety of the shellfish toxins spirolides B and D using an iterative oxidative radical cyclization strategy

The enantioselective synthesis of the bis-spiroacetal fragment of the shellfish toxins, spirolides B 1 and D 2, is reported. The carbon framework was constructed via a Barbier reaction of dihydropyran 10 with aldehyde 11, followed by two oxidative radical cyclizations to construct the bis-spiroacetal ring system. A silyl-modified Prins cyclization and enantioselective crotylation successfully installed the stereocenters in the cyclization precursor 21. The initial unsaturated bis-spiroacetals 9a-d underwent equilibration during epoxidation to trans-epoxide 24 that was converted to tertiary alcohol 7.     

Synthesis of the C10-C22 bis-spiroacetal domain of spirolides B and D via iterative oxidative radical cyclization

[reaction: see text] A synthetic approach to the novel bis-spiroacetal moiety of spirolides B and D is reported. The strategy hinges upon successive formation of the spirocenters at C15 and C18 by radical oxidative cyclization, followed by base-induced rearrangement of a C19-20 alpha-epoxide to introduce the C19 hydroxyl group.     

Synthesis of the bis-spiroacetal core of the antimitotic agent spirastrellolide B

The spirastrellolides are a family of potent antimitotic agents isolated from the marine sponge Spirastrella coccinea . Synthetic studies toward the DEF bis-spiroacetal core of spirastrellolide B are reported. A modular approach was pursued by the use of two dithiane disconnections to enable a highly convergent synthesis. The ease of lithiation and nucleophilicity of these 2-substituted-1,3-dithianes were investigated during the course of the synthesis, and the alkylations were found to proceed most efficiently at elevated temperatures. Formation of the [5,6,6]-bis-spiroacetal ring system was achieved via a double dithiane deprotection/spiroacetalization strategy.     

Synthesis of the heptapeptide of the cyclopeptide moiety of polymixin B

Conclusions The synthesis of the heptapeptideN -BOC-N -pelargonyl-L-lysyl-N -Z-L-lysyl-D-phenylalanyl-L-leucyl-N -Z-L-lysyl-N -Z-L-lysyl-L-threonine, a linear analog of the cyclopeptide part of the antibiotic polymixin B, has been effected (yield 63%). The possibility of using this method for the synthesis of peptides on a polymer support without protecting the hydroxyl group of threonine has been shown.Khimiya Prirodnykh Soedinenii, Vol. 6, No. 3, pp. 359–361, 1970     

Synthesis of a functionalized 7,6-bicyclic spiroimine ring fragment of the spirolides

The asymmetric synthesis of a functionalized 7,6-spiroimine related to the spirolides is described. Intermolecular Diels-Alder cycloaddition of a chiral trisubstituted dienophile and Danishefsky's diene enabled simultaneous installation of the C7 and C29 stereocenters. Further transformations and late-stage aza-Wittig cyclization afforded the spiroimine in good yield. During this study, an unprecedented 14-membered dialdimine was also obtained.     

Synthesis and biological activity of the hexalin moiety of compactin (ML-236B)

Alcohols14and21and the derived half-glutarate esters15and22have been prepared and evaluated as inhibitors of HMG CoA reductase. Compound14, the hexalin moiety of the natural fungal metabolite compactin (ML-236B) and compound21, its isomeric diene, have essentially no inhibitory properties. Compounds15and22show definite activity, although several orders of magnitude lower than that shown by compactin.     

Total Synthesis of Aculenes B and D

The first total synthesis of aculene D, a structurally rare nordaucane-type natural product exhibiting quorum sensing inhibitory activity, has been accomplished from a known five-membered hydroxy carboxylic acid. Nucleophilic addition of methallylzinc bromide to a β-keto aldehyde intermediate under Barbier conditions to install the secondary hydroxy group on the seven-membered ring of aculene D gave the corresponding alcohol with an undesired configuration predominantly. On the other hand, the protection of its keto group as the ethylene acetal induced a reversal of diastereoselectivity, affording a desired diastereomer in a selective manner. The construction of the seven-membered ring was realized by ring-closing metathesis using a triethylsilyl-protected monocyclic diene ester precursor. An additional five-step manipulation on the cyclization product including the installation of an ethyl group on the five-membered ring completed the synthesis of aculene D, whose esterification with an N-protected l -proline followed by deprotection also achieved the first total synthesis of aculene B.     

Synthesis of the peptide moiety of the jamaicamides

The jamaicamides, isolated from cyanobacterium Lyngbya majuscula in Jamaica, are unique mixed polyketide-peptides that are reported to be blockers of the sodium channels. The peptide moiety contains a pyrrolinone ring and a β-methoxy enone functionality. Herein, we report the stereoselective synthesis of the N-(Boc)₂-protected peptide moiety of the jamaicamides by utilizing Meldrum’s acid starting from l-alanine and N-Boc-β-alanine.     

Synthesis of the glycosyl lactol moiety of halichoblelide

The enantioselective synthesis of the 2-deoxy-α-l-fucosyl lactol moiety of halichoblelide, a potent cytotoxin isolated from an actinomycete of marine origin, was achieved using a diastereoselective addition of a dithianyl anion to a chiral aldehyde intermediate and a stereoselective glycosidation of a hydroxy lactone intermediate derived from the addition product with a protected l-fucal as the key steps.     

Synthesis of the furo-pyran moiety of azadirachtin.

9-hydroxy-dihydrofuro-2,3b-tetrahydropyran is synthesised as a model substance for azadirachtin. The key step utilizes cyclisation of hydroxy-dialdehyde precursors, followed by acetylation and pyrolysis.     

Synthesis of the 4-methyl-1,2-oxazetidine-4-carboxylic acid moiety of the originally proposed halipeptin A and B structures

O-Alkylation of N-hydroxycarbamate 6 with iodo ester 5 affords 15, which was elaborated to mesylate 4. Intramolecular N-alkylation affords methyl N-Boc-4-methyl-1,2-oxazetidine-4-carboxylate (3). The geminal coupling constant of the methylene protons is 8.5 Hz, which is much smaller than the 12.0 Hz reported for halipeptins A and B. This confirms that the halipeptins do not contain an oxazetidinecarboxylic acid as originally proposed in structure 1, but a thiazoline as in the revised structure 2. The unusual O-alkylation of 5 probably proceeds by an electron transfer mechanism.     

Synthesis of isogranulatimides A and B analogues possessing a 7-azaindole unit instead of an indole moiety

The synthesis of a new family of isogranulatimides analogues is described in which a 7-azaindole replaces the indole moiety. The key step is the photocyclization of the aza didemnimide intermediates which leads to two isomeric analogues of isogranulatimides A and B. A derivative bearing a carbohydrate part linked to the azaindole via a β-N-glycosidic bond was also prepared.     

Synthesis and protection of aryl sulfates using the 2,2,2-trichloroethyl moiety

[reaction: see text] The 2,2,2-trichloroethyl (TCE) group was utilized as the first protecting group for aryl sulfates. Aryl sulfates, protected with the TCE group, were prepared in high yield by reacting phenols with chlorosulfuric acid TCE ester. Deprotection was accomplished using Pd/C-ammonium formate or with Zn-ammonium formate to give aryl sulfate monoesters in high yield. This approach to aryl sulfate synthesis was successfully applied to the construction of estrone sulfate derivatives, which could not be prepared by previous methodologies.     

Synthesis and properties of spiro nucleosides containing the barbituric acid moiety

The two chiral spiro nucleosides 4 and 5 containing the barbituric acid moiety were efficiently synthesized from optically pure precursors, and their properties were studied. The carbocyclic nucleoside 5 is considerably more stable against ring opening than the deoxyribosyl derivative 4. Both compounds present enhanced hydrogen bonding capacity with diacetyladenosine.     

Synthesis and characterization of aromatic polyimides containing tetraphenylfuran-thiazole moiety

Journal of Thermal Analysis and Calorimetry - 2,5-Bis(4-(2-aminothiazole) phenyl)-3,4-diphenyl furan (BATPDF), well prepared in four steps. Novel aromatic polyimides containing...     

Synthesis and characterization of novel phosphoramidates containing benzimidazole moiety

Novel heterocyclic phosphoramidates were synthesized by a nucleophilic substitution reaction of 2-substitutedbenzimidazoles and diphenyl chlorophosphate (ClPO₃Ph₂) in the presence of potassium hydroxide (KOH) under an argon atmosphere. The structures of the phosphoramidates were characterized by NMR, IR, melting point, and elemental analysis.     

Synthesis and antimicrobial activity of some new 1,3,4-thiadiazole and 1,2,4-triazole compounds having a D,L-methionine moiety

New 1,3,4-thiadiazole, 5a-e, and 1,2,4-triazolecompounds 6a-c, containing a D,L-methionine moiety were synthesized by intramolecular cyclization of 1,4-disubstituted thiosemicarbazides 4a-e in acid and alkaline media, respectively. The potential antimicrobial effects of the synthesized compounds were investigated using the Staphylococcus aureus ATCC 25923, Bacillus antracis ATCC 8705, Bacillus cereus ATCC 10987, Sarcina lutea ATCC 9341 and Escherichia coli ATCC 25922 strains. The newly synthesized compounds exhibited promising activities against Bacillus antracis and Bacillus cereus.