Stereocontrolled synthesis of steroid side chain; stereoselective syntheses of cholesterol and 25-hydroxycholesterol

Novel stereoselective method to introduce side chain onto 17-oxosteroids has been deviced, and using the method cholesterol and 25-hydroxycholesterol are synthesized.     

Total synthesis and stereochemical reassignment of the indole alkaloid vinoxine

The first total synthesis of the indole alkaloid vinoxine and the reassignment of the relative configuration at carbon-16 in this alkaloid is reported.     

Total synthesis and absolute stereochemical assignment of kibdelone C

Kibdelones are hexacyclic tetrahydroxanthones and potent anticancer agents isolated from an Australian microbe. Herein, we describe the synthesis of a chiral, nonracemic iodocyclohexene carboxylate EF ring fragment of the kibdelones employing an intramolecular iodo halo-Michael aldol reaction and its merger with an ABCD ring fragment to afford the congener kibdelone C.     

Stereocontrolled synthesis of the ABCDE ring moiety of ciguatoxin CTX3C

The ABCDE ring moiety of ciguatoxin CTX3C, a major causative agent of ciguatera poisoning, was stereoselectively synthesized. The key transformations are a chiral auxiliary-based asymmetric alkylation and an asymmetric aldol condensation, which controlled the formation of the C11 and C21-stereocenters, respectively. A highly practical and efficient route to the ABCD ring fragment, a common precursor for the divergent synthesis of the left wings of ciguatoxins, was also established.     

Total synthesis of dipiperamide A and revision of stereochemical assignment

The first total synthesis of dipiperamide A has been achieved by employing a solid-state photodimerization of an (E)-cinnamic acid derivative. This critical step results in the cyclobutane ring, which exists in the natural product, with full control of the regio- and stereochemistry at the four stereogenic centers. Results from these studies indicate that the proposed stereostructure of natural dipiperamide A should be revised to the structure originally assigned to dipiperamide B.     

Azedaralide: total synthesis, relative and absolute stereochemical assignment

Azedaralide, a potentially advanced intermediate for the total synthesis of various tetranortriterpenes, was constructed utilising the Fernández-Mateos protocol and assigned both relative and absolute stereochemistries. Both asymmetric aldol and classical chiral resolution attempts failed to deliver pure enantiomers whereas preparative chiral chromatography resolved racemic azedaralide with ease.     

Total synthesis and stereochemical assignment of the spiroisoxazoline natural product (+)-calafianin

[STRUCTURE: SEE TEXT] Synthesis of the spiroisoxazoline natural product (+)-calafianin is reported using asymmetric nucleophilic epoxidation and nitrile oxide cycloaddition as key steps. Synthesis and spectral analysis of all calafianin stereoisomers led to unambiguous assignment of relative and absolute stereochemistry.     

Perylene bisimide atropisomers: synthesis, resolution, and stereochemical assignment

The macrocyclization of the tetra-hydroxyphenoxy-substituted perylene bisimide 4 bearing two (R)-configured 2-octyl substituents in the imide positions by etherification with diethylene glycol ditosylate afforded both the diagonally bridged (1,7- and 6,12-linkage) and laterally bridged (1,12- and 6,7-linkage) regioisomers 6 and 7. The atropo-diastereomers of the diagonally bridged macrocycle 6 were separated by semipreparative HPLC on a chiral column, and their absolute configurations were determined by circular dichroism (CD) spectroscopy in combination with quantum chemical CD calculations. The isolated epimers (P,R,R)-6 and (M,R,R)-6 represent the first examples of diasteriomerically pure perylene bisimide atropisomers. The optical and chiroptical properties of these epimers were investigated by UV/vis, fluorescence, and CD spectroscopy, and their conformational properties have been explored by temperature-dependent 1H NMR studies.     

Total synthesis, stereochemical assignment, and antimalarial activity of gallinamide A

The total synthesis and stereochemical assignment of gallinamide A, an antimalarial depsipeptide of cyanobacterial origin, is described. Synthesis of the four possible N-terminal diastereoisomers of gallinamide A (including the natural product symplostatin 4) was achieved using a divergent strategy from a common imide fragment. The natural product and corresponding diastereoisomers were synthesized in 30-33% overall yield in a longest linear sequence of 8 steps. Comparative NMR spectroscopic studies of the four synthetic diastereoisomers with the isolated natural product demonstrated that gallinamide A possesses a dimethylated L-isoleucyl residue at the N-terminus. As such, we have shown that gallinamide A is structurally and stereochemically identical to symplostatin 4. Gallinamide A and its N-terminal diastereoisomers were also shown to possess significant antimalarial activity with IC(50) values in the nanomolar range against the 3D7 strain of Plasmodium falciparum.     

Total synthesis,stereochemical assignment,and biological evaluation of L-755,807

The relative and absolute configurations of L-755,807 were established through total synthesis. All four possible stereoisomers were prepared via a convergent synthetic strategy, including a novel diastereoselective Darzens reaction of an α-alkoxy aldehyde with di-tert-butyl bromomalonate, an E-selective Horner–Wadsworth–Emmons reaction, and late-stage coupling of the ring and side-chain segments. Additionally, biological evaluation of the synthesized compounds revealed their potent inhibitory activities (IC₅₀?=?5–21?μM) against amyloid-β aggregation for the treatment of Alzheimer's disease.     

The indole side chain of tryptophan as a versatile pi-donor

Single-armed, 15- and 18-membered lariat ether receptor systems having indolylethyl side arms bind Na+ and K+ in the ring. The indole residue serves as a pi-donor to the ring-bound cation. Whether the five- or six-membered ring interacts most directly with Na+ or K+ depends on whether the sidearm is attached to indole's 3- or 5-position. This suggests that structural as well as electronic factors are important in pi-complexation of alkali metal cations.     

Full stereochemical assignment and synthesis of the potent anthelmintic pyrrolobenzoxazine natural product CJ-12662

The structure of the unusual anthelmintic pyrrolobenzoxazine terpenoid natural product CJ-12662 was established by X-ray crystallography and partial synthesis from 2-chloronitrobenzene. An unusual Meisenheimer-type rearrangement was used to provide the core pyrrolobenzoxazine heterocycle, and coupling of a tetracyclic pyrrolobenzoxazine lactone with the terpene alcohol was used to complete the synthesis of CJ-12662.     

Stereocontrolled synthesis of the aminocyclitol moiety of (+)-trehazolin via C-H insertion reaction of alkylidenecarbene

The aminocyclitol moiety of (+)-trehazolin, a powerful trehalase inhibitor, was synthesized in a stereocontrolled manner from cis-2-butene-1,4-diol via C-H insertion reaction of the alkylidenecarbene, followed by regioselective opening of the epoxide ring. It was obtained in an enantiomerically pure form by twice using Sharpless asymmetric epoxidation.     

Amino acid derivatives, VIII [1]: synthesis and antimicrobial evaluation of α-amino acid esters bearing an indole side chain

A series of peptide and dipeptide derivatives conjugated with an indole residue were synthesized. The prepared compounds were tested for antimicrobial activity against two different bacterial and one antifungal species displaying different degrees of antimicrobial activities or inhibitory actions. Correspondence: Adel A.-H. Abdel-Rahman, Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koam, Egypt.     

Total synthesis and stereochemical assignment of burkholdac B, a depsipeptide HDAC inhibitor

Three diastereomers of burkholdac B were prepared by total synthesis, enabling the full stereochemical assignment of the natural product. It is proposed that burkholdac B is identical to thailandepsin A independently isolated by Cheng from the same strain of Burkholderia thailandensis . Burkholdac B is the most potent among depsipeptide histone deacetylase inhibitors in growth inhibition of the MCF7 breast cancer cell line with an IC(50) of 60 pM.     

Design,synthesis, resolution,and stereochemical assignment of a conformationally rigid chiral ligand derived from anthracene and a dienophile containing a pyridine moiety

The conformationally rigid chiral ligand, trans-12-(pyridin-2-yl)-9,10-dihydro-9,10-ethanoanthracene-11-carboxylic acid ethyl ester, 1, was designed and synthesized in racemic form. Both isomers were successfully obtained in enantiomerically pure form through classical resolution using l-(+)-tartaric acid in acetonitrile. The nature of the diastereomeric complex formed in this resolution was elucidated using single crystal X-ray crystallographic studies. The absolute configuration of (+)-1 was unambiguously assigned as (11S,12S) by single crystal structural analysis of salt 5 formed from (+)-1 and l-(+)-tartaric acid.     

Stereocontrolled synthesis and configurational assignment of (R)-all-trans-11,12-dihydro-3-hydroxyretinol

The synthesis of (R)-all-trans-11,12-dihydro-3-hydroxyretinol and putative metabolites of the side-chain functional group has been achieved in a stereocontrolled manner via the Suzuki-Hiyama cross-coupling reaction of an enantiopure (hydroxycyclohexenyl)alkenyliodide and non-conjugated pinacolboranedienoate, which allowed the absolute configuration of this natural product to be confirmed.     

Total synthesis and stereochemical assignment of the salicylate antitumor macrolide lobatamide C(1)

The total synthesis and stereochemical assignment of the potent antitumor macrolide lobatamide C is reported. The synthesis involves Cu(I)-mediated enamide formation and Na(2)CO(3)-mediated esterification of a beta-hydroxy acid and a salicylate cyanomethyl ester. Macrolactonization was accomplished using a Mitsunobu protocol. The stereochemical assignment of lobatamide C was achieved by Mosher ester analysis and comparison with prepared stereoisomers.