Enantioselective total synthesis and stereochemical revision of communiols E and F

The enantioselective total synthesis of candidate structures for communiols E and F, novel bicyclic polyketides of fungal origin, was accomplished using a Lewis acid-mediated ring closure reaction of an allylsilane intermediate as the key step. Comparison of the spectral data of the synthetic materials with those of natural communiols E and F, coupled with biosynthetic considerations, led to the conclusion that the stereochemistry of communiols E and F should be (2S,5S,7R, 8S,11R)- and (5S,7R,8S,11R)-forms, respectively.     

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 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 sacrolide A

An enantioselective total synthesis of sacrolide A, an antimicrobial and cytotoxic fourteen-membered macrolactonic oxylipin isolated from an edible freshwater cyanobacterium, has been accomplished from a known carboxylic acid in 20% overall yield by a concise ten-step sequence. The key transformations include chiral oxazolidinone-based diastereoselective installation of two hydroxy-bearing stereocenters, the Horner–Wadsworth–Emmons olefination to construct the full carbon skeleton, and the Shiina macrolactonization to establish the fourteen-membered macrolide structure.     

Enantioselective total synthesis of batzelladine F and definition of its structure

Batzelladine F (1) was synthesized in enantioselective and stereoselective fashion in 15 steps (longest linear sequence) and 1.7% overall yield from two readily available enantioenriched beta-hydroxy esters, methyl (R)-3-hydroxydecanoate and methyl (R)-3-hydroxybutyrate. Tethered Biginelli condensations are used to assemble both tricyclic guanidine fragments, with the second tethered Biginelli condensation (14 + 16 --> 17) also being employed to join the guanidine fragments. Three diastereomers of batzelladine F, 2-4, were prepared also. A combination of HPLC, optical rotation and CD spectroscopy was employed to distinguish stereoisomers 1-4, proving that 1 is the correct structure of the hexacyclic marine alkaloid batzelladine F.     

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 total synthesis of 1-epi-pathylactone A

[structure: see text]. The first enantioselective total synthesis of 1-epi-pathylactone A, 3, has been accomplished using a PhI(OAc)2-mediated domino reaction as a key step. No diastereomeric separation was required throughout the whole synthetic scheme presented in this paper. Comparison of 1H and 13C NMR spectral data of the synthetic product with the reported spectral data of natural pathylactone A, coupled with an X-ray crystallographic analysis, led to the conclusion that the C1 configuration in the original paper was erroneously ascribed to (R).     

Enantioselective total synthesis of eunicenone A.

An enantioselective, stereocontrolled total synthesis of eunicenone A (1) is described starting from geranylgeranylacetylene (9) in 14 steps via intermediates 10-20. The most critical construction in the synthesis is the highly effective Diels-Alder combination of the achiral components 2-bromoacrolein and diene 13 in the presence of the chiral Lewis acid catalyst 14 to form 15 (85% yield, 97% ee, >98:2 endo-exo ratio). The synthesis utilizes a novel reagent (12) for introduction of silicon, which serves to activate and direct the diene 13 for Diels-Alder reaction and to provide for eventual oxygen functionality of homoallylic alcohol 17 under mild conditions. Other noteworthy steps include the position selective and diastereoselective epoxidation 17 --> 18, the methoxycarbonylation with allylic transposition 19 --> 20, and the alpha,beta-enone unmasking 20 --> 1.     

Enantioselective total synthesis of (+)-sarcandralactone A

An enantioselective total synthesis of the lindenane sesquiterpene (+)-sarcandralactone A has been accomplished for the first time. The synthesis features a SeO₂-mediated [2,3]-sigmatropic rearrangement for the facile construction of the tertiary allylic alcohol as a single diastereoisomer.     

Enantioselective total synthesis of macrosphelides A and E

Enantioselective synthesis of 16-membered trilactone macrolides, macrosphelide A and E from (S)-lactic acid is described. Key features of the synthesis include the utility of a hitherto unexplored β-ketophosphonate derived from lactic acid and Yamaguchi lactonization leading to the title compounds.     

Enantioselective total synthesis of (+)-rogioloxepane A

[reactiojn: see text] The enantioselective synthesis of (+)-rogioloxepane A has been achieved in 21 steps from 1,5-hexadien-3-ol. The key steps in the synthesis are an asymmetric glycolate alkylation leading to the diene 2 and a subsequent ring-closing metathesis to construct the oxepene core.     

Enantioselective total synthesis of cyathin A3

The total synthesis of (-)-cyathin A3 is described. The key step involves an unusual enantioselective Diels-Alder reaction of 2,5-dimethyl-1,4-benzoquinone with 2,4-bis(trimethylsilyloxy)-1,3-pentadiene, using Mikami's catalyst [(R)-BINOL + Cl2Ti(OiPr)2 + 4 A mol sieves] modified by addition of Mg and SiO2. Because cyathin A3 is easily transformed into allocyathin B3, cyathin B3, cyathin C3, and neoallocyathin A4, this route also constitutes formal syntheses of these natural products.     

Enantioselective total synthesis of pteridic acid A

Pteridic acid A, a potent plant growth promoter with auxin-like activity, was synthesized enantioselectively by using the Evans asymmetric aldol reaction as the key C-C bond forming step.     

Enantioselective total synthesis of briarellins E and F: the first total syntheses of briarellin diterpenes

Enantioselective total syntheses of briarellin E (4) and briarellin F (5) have been achieved starting with (S)-(+)-carvone and (S)-(-)-glycidol. These total syntheses are the first of briarellin diterpenes. The central step in these syntheses is acid-promoted condensation of cyclohexadienyl diol 15 and (Z)-alpha,beta-unsaturated aldehyde 16 to form, with complete stereocontrol, the hexahydroisobenzofuran core and six stereocenters of these coral metabolites. These syntheses also feature stereospecific photolytic deformylation of beta,gamma-unsaturated aldehyde 17 to remove the extraneous carbon introduced in the Prins-pinacol step, chemo- and stereoselective hydroxyl-directed epoxidation of dienyl alcohol 18 to incorporate the C3 oxygen stereocenter, regio- and stereoselective rearrangement of epoxy ester 19 to install the C4 oxygen substituent, efficient dehydrative cyclization of a 1,6-diol intermediate to form the oxepane ring, and diastereoselective Nozaki-Hiyama-Kishi cyclization of vinyl iodide aldehyde 25 to forge the oxacyclononane ring and the C6 hydroxyl stereocenter. These total syntheses establish the absolute configurations of 4 and 5, define a concise strategy for the total synthesis of briarellin diterpenes, and provide additional illustrations of the uncommon utility of pinacol-terminated cationic cyclizations for stereocontrolled synthesis of complex oxacyclic natural products.     

Enantioselective total synthesis of aplyviolene

The enantioselective total synthesis of the rearranged spongian diterpene aplyviolene has been completed in 14 steps from the known hydroazulenone 8. The key junction of the hydrocarbon and oxygenated fragments to form the critical C8 quaternary carbon stereocenter and set the stage for elaborating the delicate bicyclic lactone functionality was accomplished in high yield and exquisite stereoselectivity by Michael addition of an enantioenriched hydroazulenone enolate to an enantiopure α-bromocyclopentenone.     

Enantioselective total synthesis of (+)-leucascandrolide A macrolactone

[reaction: see text] The enantioselective synthesis of the (+)-leucascandrolide A macrolactone has been achieved in 20 linear steps from 1,3-propanediol. The key steps in the synthesis are a reductive cleavage of bicyclic ketal 5 to establish the C15 stereogenic center and a diastereoselective aldol of the boron enolate of methyl ketone 3 to aldehyde 4 in preparation for a heteroconjugate addition for the introduction of the C3 stereocenter.