Access to Enantiopure 4‑Substituted 1,5-Aminoalcohols from Phenylglycinol-Derived δ‑Lactams: Synthesis of <i>Haliclona</i> Alkaloids

LiNH₂BH₃-promoted reductive opening of 8-substituted phenylglycinol-derived oxazolopiperidone lactams leads to enantiopure 4-substituted-5-aminopentanols, which are used as starting building blocks in the synthesis of the <i>Haliclona</i> alkaloids haliclorensin C, haliclorensin, and halitulin (formal). The starting lactams are easily accessible by a cyclocondensation reaction of (<i>R</i>)-phenylglycinol with racemic γ-subtituted δ-oxoesters, in a process that involves a dynamic kinetic resolution

Preparation and Double Michael Addition Reactions of a Synthetic Equivalent of the Nazarov Reagent

A synthetic equivalent of the Nazarov reagent, the silyl derivative <b>2</b>, able to undergo base-catalyzed double Michael addition reactions with α,β-unsaturated carbonyl compounds has been developed. The new reagent satisfactorily reacts with unsaturated indolo[2,3-<i>a</i>]quinolizidine lactams to give pentacyclic yohimbinone-type derivatives

A Practical Synthetic Route to Enantiopure 6-Substituted <i>cis</i>-Decahydroquinolines

Starting from 4-substituted cyclohexanones, a practical synthetic route to enantiopure 6-substituted <i>cis</i>-decahydroquinolines has been developed, the key steps being a stereoselective cyclocondensation of an unsaturated δ-keto ester derivative with (<i>R</i>)-phenylglycinol and the stereoselective hydrogenation of the resulting tricyclic oxazoloquinolone lactams

Enantioselective Total Synthesis of Fluvirucinin B₁

A convergent synthesis of fluvirucinin B₁ from acid <i>ent</i>-<b>6a</b> and nitrile <i>ent</i>-<b>9</b>, involving an organocopper coupling, a stereoselective allylation, a ring-closing metathesis reaction, and a stereoselective hydrogenation as the key steps, is reported. The starting building blocks have been prepared in a straightforward manner from a common phenylglycinol-derived lactam <b>1</b>. An unprecedented regioselective oxidation of phenylglycinol-derived secondary amines <b>5</b> to carboxylic acids <b>6</b> has been developed

Enantioselective Total Synthesis of (+)-Gephyrotoxin 287C

A synthesis of (+)-gephyrotoxin 287C using (<i>S</i>)-phenylglycinol-derived tricyclic lactam <b>7</b> as the starting enantiomeric scaffold is reported. From the stereochemical standpoint, the key steps are the generation of the DHQ C-5 stereocenter by hydrogenation of the C–C double bond, removal of the chiral inductor to give a <i>cis</i>-DHQ, introduction of the DHQ C-2 substituent, completion of the (<i>Z</i>)-enyne moiety, and generation of the C-1 stereocenter during closure of the pyrrolidine ring

Preparation and Double Michael Addition Reactions of a Synthetic Equivalent of the Nazarov Reagent

A synthetic equivalent of the Nazarov reagent, the silyl derivative <b>2</b>, able to undergo base-catalyzed double Michael addition reactions with α,β-unsaturated carbonyl compounds has been developed. The new reagent satisfactorily reacts with unsaturated indolo[2,3-<i>a</i>]quinolizidine lactams to give pentacyclic yohimbinone-type derivatives

Stereoselective Total Synthesis of the Putative Structure of Nitraraine

After the structure originally proposed for nitraraine was shown to be incorrect by total synthesis, the alternative structure <b>5</b> was recently suggested for the alkaloid on biosynthetic grounds and by comparison with the ¹H NMR data of tangutorine. The unambiguous synthesis of <b>5</b> is reported from tryptophanol and ketodiester <b>6</b>, via oxazoloquinolone lactam <b>7</b>. However, the melting point and ¹H NMR data of <b>5</b> did not match those reported for the natural product

Studies on the Synthesis of Phlegmarine-Type <i>Lycopodium</i> Alkaloids: Enantioselective Synthesis of (−)-Cermizine B, (+)-Serratezomine E, and (+)-Luciduline

The synthesis of the <i>Lycopodium</i> alkaloids, (−)-cermizine B, (+)-serratezomine E, and (+)-luciduline using phenylglycinol-derived tricyclic lactams as chiral scaffolds, is reported. The requisite lactams are prepared by a cyclocondensation reaction between (<i>R</i>)- or (<i>S</i>)-phenylglycinol and the substituted δ-keto ester <b>11</b>, easily accessible from (<i>R</i>)-pulegone. The factors governing the stereoselectivity of these cyclocondensation reactions are discussed. Key steps of the synthesis from the stereochemical standpoint are the stereoselective elaboration of the allyl substituent to the (<i>S</i>)-2-(piperidyl)­methyl moiety and the stereoselective removal of the chiral inductor to give a <i>cis</i>-decahydroquinoline

Studies on the Synthesis of Phlegmarine-Type <i>Lycopodium</i> Alkaloids: Enantioselective Synthesis of (−)-Cermizine B, (+)-Serratezomine E, and (+)-Luciduline

The synthesis of the <i>Lycopodium</i> alkaloids, (−)-cermizine B, (+)-serratezomine E, and (+)-luciduline using phenylglycinol-derived tricyclic lactams as chiral scaffolds, is reported. The requisite lactams are prepared by a cyclocondensation reaction between (<i>R</i>)- or (<i>S</i>)-phenylglycinol and the substituted δ-keto ester <b>11</b>, easily accessible from (<i>R</i>)-pulegone. The factors governing the stereoselectivity of these cyclocondensation reactions are discussed. Key steps of the synthesis from the stereochemical standpoint are the stereoselective elaboration of the allyl substituent to the (<i>S</i>)-2-(piperidyl)­methyl moiety and the stereoselective removal of the chiral inductor to give a <i>cis</i>-decahydroquinoline

Model Studies on the Synthesis of Madangamine Alkaloids. Assembly of the Macrocyclic Rings

Using simplified model derivatives, the assembly of the macrocyclic rings of madangamines, including the 13- and 14-membered D rings of madangamines C–E, the all-<i>cis</i>-triunsaturated 15-membered D ring of madangamine A, and the (<i>Z</i>,<i>Z</i>)-unsaturated 11-membered E ring common to madangamines A–E, has been studied