Total synthesis of attenols A and B

A concise approach for the total synthesis of attenols A and B is described involving MacMillan’s α-aminooxylation, Evan’s asymmetric alkylation, Brown’s allylation, and spiro-ketalization as key steps. This approach has successfully demonstrated the α-aminooxylation protocol for the construction of the anti-1,3-diol unit.     

Enantioselective total synthesis of litseaverticillols A and B

[reaction: see text] The first enantioselective total synthesis of the (1R,5S)-stereoisomer of litseaverticillols A and B, anti-HIV monocyclic sesquiterpenoids isolated from a perennial shrub found in Vietnam, was accomplished in six steps from homogeranic acid by employing the Evans asymmetric aldol reaction and a microwave-promoted cyclization of a stannylated thiol ester intermediate as the C-C bond-forming steps.     

Enantioselective synthesis of stephacidin B

We describe an enantioselective synthetic route to the antiproliferative alkaloid stephacidin B (1) proceeding in 18 steps and 4.0% yield from 4,4-(ethylenedioxy)-2,2-dimethylcyclohexanone (3). Key features of the synthetic sequence include the use of the Corey-Bakshi-Shibata (CBS) reduction to introduce asymmetry early in the synthetic route, use of the novel electrophile N-(tert-butoxycarbonyl)-5-(isopropylsulfonyloxymethyl)-2,3-dihydropyrrole in a stereoselective enolate alkylation, a diastereoselective Strecker-type addition of hydrogen cyanide to an N-Boc enamine substrate in the solvent hexafluoroisopropanol, platinum-catalyzed nitrile hydrolysis under neutral conditions, cyclization of an acylamino radical intermediate to form the diketopiperazine core of stephacidin B, and implementation of a convergent procedure for introduction of the key 3-alkylidene-3H-indole 1-oxide functional group in the final stage of the route to prepare the structure 2, previously proposed to be the fungal metabolite avrainvillamide (17 steps, 4.2% yield). We observed that synthetic (-)-2 dimerized in the presence of triethylamine to form (+)-stephacidin B (>95%). We also obtained evidence that 2 can form 1 under mild conditions, and that 2 reacts with nucleophiles, such as methanol, by conjugate addition.     

Enantioselective synthesis and absolute configurations of aculeatins A and B

The two naturally occuring, bioactive spiroacetals aculeatins A and B have been synthesized for the first time in enantiopure form using an asymmetric allylation as the only chirality source. A further key step was a stereoselective aldol reaction with remote induction. The absolute configurations of the natural products have been established and the previously assigned relative configurations have been corrected.     

Enantioselective total synthesis of cineromycin B

The enantioselective total synthesis of cineromycin B, a 14-membered unsaturated macrolide with two doubly allylic alcohols, was completed using a Julia coupling, an oxidative [2,3]-sigmatropic rearrangement of selenide, and a Yamaguchi macrolactonization as key reactions.     

Enantioselective total synthesis of heliespirone B

The first enantiocontrolled total synthesis of heliespirone B has been accomplished employing a biomimetic intramolecular oxy-Michael reaction followed by the regio- and diastereoselective reduction of the carbonyl function as key steps.     

Enantioselective synthesis of (−)-barrenazines A and B

A short enantioselective synthesis of barrenazines A and B is described. Barrenazines A and B are prepared following a common synthetic route in nine steps (19% overall yield) and eight steps (21% overall yield), respectively, from readily available 4-methoxy-3-(triisopropylsilyl)pyridine. The synthesis relies on a highly diastereoselective nucleophilic addition of a Grignard reagent to a chiral acylpyridinium salt, a radical azidation of a silyl enol ether and the assembly of the pyrazine ring by reductive dimerization of a functionalized 5-azidopiperidin-4-one.     

Enantioselective total synthesis of convolutamydines B and E

[reaction: see text] The first enantioselective total synthesis of convolutamydines B and E has been achieved using our vinylogous Mukaiyama aldol reaction. The synthesis features highly diastereoselective vinylogous Mukaiyama aldol reaction with isatin instead of aldehydes to construct a chiral center of convolutamydines. Additionally, the absolute configuration of natural convolutamydine B has been determined as R by its CD spectrum.     

Enantioselective total synthesis of (+)-salvileucalin B

An enantioselective total synthesis of the diterpenoid natural product (+)-salvileucalin B is reported. Key findings include a copper-catalyzed arene cyclopropanation reaction to provide the unusual norcaradiene core and a reversible retro-Claisen rearrangement of a highly functionalized norcaradiene intermediate.     

Enantioselective synthesis of marine indole alkaloid hamacanthin B

An enantioselective total synthesis of hamacanthin B (1) is described. This synthesis is based on the asymmetric synthesis of (S)-2-azido-(indol-3-yl)ethylamine 7, which is coupled with the 3-indolyl-alpha-oxoacetyl chloride 8 and subsequently used in a successful intramolecular Staudinger-aza Wittig cyclization to form the central dihydropyrazinone ring. The stereochemistry of naturally isolated hamacanthin B is revealed as the (S)-configuration.     

Enantioselective total synthesis of (R)-strongylodiols A and B

We describe an expeditious enantioselective total synthesis of the acetylenic marine natural products (R)-strongylodiols A and B. Central to the strategy is the use of Zn(OTf)₂, amine base, and N-methyl ephedrine to mediate the direct addition of a 1,3-diyne to two long-chain aliphatic aldehydes in useful selectivities and yields.     

Enantioselective synthesis of two key intermediates for leukotrienes A_4 and B_4

Leukotrienes, arachidonic acid derived metabolites of great biological signifi-cance, are present in tissue at extremely low concentrations, so that experimentalquaatities are only accessible by chemical synthesis. In various synthetic routes,[S,S-(E)]-3-(hydroxymethyl) oxiranebutanoic acid methyl ester (1) and (S)-5-(ben-zoyloxy)-6-oxohexanoic acid methyl ester (2) have been frequently used as the C_1-C_7 fragment of LTA_4 3 and the C_1-C_6 fragment of LTB_4 4, respectively. (Scheme1)     

Enantioselective total synthesis of (−)-myrifabral A and B

A catalytic enantioselective approach to the Myrioneuron alkaloids (−)-myrifabral A and (−)-myrifabral B is described. The synthesis was enabled by a palladium-catalyzed enantioselective allylic alkylation, that generates the C(10) all-carbon quaternary center. A key N-acyl iminium ion cyclization forged the cyclohexane fused tricyclic core, while vinyl boronate cross metathesis and oxidation afforded the lactol ring of (−)-myrifabral A. Adaptation of previously reported conditions allowed for the conversion of (−)-myrifabral A to (−)-myrifabral B.

A catalytic enantioselective approach to the Myrioneuron alkaloids (−)-myrifabral A and (−)-myrifabral B is described.     

Enantioselective synthesis of aurisides A and B, cytotoxic macrolide glycosides of marine origin

The enantioselective synthesis of aurisides A and B, macrolide glycosides of marine origin, was achieved by a convergent approach. The C1-C9 segment 4 was prepared from (R)-pantolactone, and the C10-C17 segment 14 was synthesized from (R)-glycidyl trityl ether. The Nozaki-Hiyama-Kishi reaction between 4 and 14 and subsequent reactions gave seco acid 10, which was converted into the aglycon (3) of aurisides by construction of the 14-membered lactone and bromine-substituted conjugated diene. The glycosylation reaction of the aglycon provided aurisides A and B.     

Enantioselective total synthesis of (-)-erinacine B

The first enantioselective total synthesis of (-)-erinacine B has been achieved. Our approach features convergent construction of the 5-6-7 tricyclic cyathane core system via chiral building blocks prepared using asymmetric catalysis developed by us and highly stereoselective construction of all stereogenic centers in the aglycon. [reaction: see text].     

Enantioselective total synthesis of (-)-clavosolide B

Enantioselective synthesis of 2, a revised structure for (-)-clavosolide B, was accomplished by a convergent approach, where syn-selective aldol, hydroxy-directed cyclopropanation, Mitsunobu inversion, Schmidt-type glycosylation, and macrolactonization reactions were utilized as key reactions. Comparison of 1H and 13C NMR spectra and optical rotation measurement confirmed the relative and absolute stereochemistry of clavosolide B (2).     

Enantioselective total synthesis of bistramide A

The enantioselective synthesis of bistramide A has been achieved with a longest linear sequence of 18 steps. The synthetic strategy involves the use of a distereoselective glycolate alkylation, an aldol addition of a chlorotitanium enolate of N-acylthiazolidinthione, and a Sharpless asymmetric epoxidation to synthesize the three key fragments.     

Enantioselective total synthesis of callipeltoside A

An asymmetric total synthesis of callipeltoside A has been accomplished highlighted by a catalytic enantioselective vinylogous aldol reaction and a boron-mediated anti-aldol reaction influenced by remote stereocontrol.     

Enantioselective total synthesis of pyrinodemin A

Pyrinodemin A 1, a cytotoxic marine alkaloid, was synthesized in a convergent and enantioselective fashion. The key steps are an asymmetric intramolecular dipolar cycloaddition of an oxazoline N-oxide to introduce the bicyclic ring system of the molecule, a cuprate coupling for the extension of the saturated chain and a B-alkyl Suzuki coupling for the introduction of a 3-pyridyl moiety. Reductive amination allowed the coupling of the second side-chain onto the nitrogen atom to give 1. Additionally, attempts to prepare 1 from a trienic precursor by a double B-alkyl Suzuki reaction are described.     

Enantioselective formal synthesis of palmerolide A

Enantioselective formal synthesis of macrolactone palmerolide A, a polyketide marine natural product, is described. Key strategies in the synthesis include the oxidative furan ring-opening of a chiral furyl carbinol for the installation of the 1,4-dienol core and a Jung nonaldol-aldol reaction for the dienamide core.