Total Synthesis of Swinholide A: An Exposition in Hydrogen-Mediated C–C Bond Formation

Diverse hydrogen-mediated C–C couplings enable construction of the actin-binding marine polyketide swinholide A in only 15 steps (longest linear sequence), roughly half the steps required in two prior total syntheses. The redox-economy, chemo- and stereo­selectivity embodied by this new class of C–C couplings are shown to evoke a step-change in efficiency

Highly Enantioselective Total Synthesis of (+)-Isonitramine

A new efficient enantioselective synthetic method of (+)-isonitramine is reported. (+)-Isonitramine was obtained in 12 steps (98% ee and 43% overall yield) from δ-valerolactam <i>via</i> enantioselective phase-transfer catalytic alkylation, Dieckman condensation, and diastereoselective reduction as key steps

Enantioselective Synthesis of (+)-Coerulescine by a Phase-Transfer Catalytic Allylation of Diphenylmethyl tert-Butyl alpha-(2-Nitrophenyl)Malonate

A 7-step enantioselective synthetic method for preparing (S)(+)-coerulescine is reported through the use of diphenylmethyl tert-butyl alpha-(2-nitrophenyl)malonate (16% overall yield, &gt;99% ee). Allylation is the key step under phase-transfer catalytic conditions (86% ee). This synthetic method can be used as a practical route for the synthesis of various derivatives of (S)(+)-coerulescine for analyzing its structure-activity relationships against its biological activities.Y

Total Synthesis of Melicoptelines C-E: Antiviral Cyclopeptides Containing a Hexahydropyrrolo[2,3-b]indole Moiety

Melicoptelines, natural cyclopeptides containing a 3a-hydroxy hexahydropyrrolo[2,3-b]indole (HPI) moiety, exhibit anti-influenza activity. Herein, we report the first total synthesis of melicoptelines C???E (1???3, respectively). The core 3a-hydroxy HPIs were synthesized in a diastereoselective manner from L- tryptophan using dimethyldioxirane-mediated oxidation. Subse-quently, sequential peptide couplings and cyclization completed the synthesis of melicoptelines C???E and unnatural melicopteline 4. The synthesized melicoptelines were evaluated for their anti -influenza activity, and melicopteline E showed the most potent inhibition of cytopathic effects. &lt;comment&gt;Superscript/Subscript Available&lt;/commentN

Enantioselective Synthesis of Chiral α‑Azido and α‑Aryloxy Quaternary Stereogenic Centers via the Phase-Transfer-Catalyzed α‑Alkylation of α-Bromomalonates, Followed by S_N2 Substitution

A new efficient synthetic method for chiral α-azido-α-alkylmalonates and α-aryloxy-α-alkylmalonates was developed. The enantioselective α-alkylation of diphenylmethyl <i>tert</i>-butyl α-bromomalonate under phase-transfer catalytic conditions [(<i>S</i>,<i>S</i>)-3,4,5-trifluorophenyl-NAS bromide, 50% KOH, toluene, and −40 °C) provided the corresponding α-bromo-α-alkylmalonates in high chemical yields (≤98%) and high optical yields (≤99% ee). The resulting α-alkylated products were converted to α-azido-α-alkylmalonates (≤96%, ≤97% ee) and α-aryloxy-α-alkylmalonates (≤79%, ≤93% ee) by S_N2 substitution with sodium azide and aryloxides, respectively

Enantioselective Synthesis of Chiral α‑Thio-Quaternary Stereogenic Centers via Phase-Transfer-Catalyzed α‑Alkylation of α‑Acylthiomalonates

An efficient synthetic method for establishing chiral α-thio-α-quaternary stereogenic center was successfully developed. The enantioselective α-alkylation of α-acylthiomalonates under phase-transfer catalytic conditions [50% aq. KOH, toluene, −20 °C, and (<i>S</i>,<i>S</i>)-3,4,5-trifluorophenyl-NAS bromide] provided the corresponding α-acylthio-α-alkylmalonates in high chemical yields (up to 99%) and high optical yields (up to 98% ee)

Enantioselective Synthesis of Chiral α‑Thio-Quaternary Stereogenic Centers via Phase-Transfer-Catalyzed α‑Alkylation of α‑Acylthiomalonates

An efficient synthetic method for establishing chiral α-thio-α-quaternary stereogenic center was successfully developed. The enantioselective α-alkylation of α-acylthiomalonates under phase-transfer catalytic conditions [50% aq. KOH, toluene, −20 °C, and (<i>S</i>,<i>S</i>)-3,4,5-trifluorophenyl-NAS bromide] provided the corresponding α-acylthio-α-alkylmalonates in high chemical yields (up to 99%) and high optical yields (up to 98% ee)