Total Synthesis of (+)‐ and (±)‐Hosieine A

Described herein is a concise total synthesis of the highly potent nicotinic acetylcholine receptor ligand hosieine A in racemic and enantioenriched forms. The synthesis requires only seven steps and features a telescoped reaction sequence initiated by a gold‐catalyzed Rautenstrauch reaction.     

Total Synthesis of (−)‐Nakadomarin A

A highly efficient 12‐step synthesis of the marine alkaloid (?)‐nakadomarin A has been accomplished. The key advanced intermediate, a tetracyclic ketone derivative, was constructed in just seven steps using a sequence that includes an asymmetric Pauson–Khand reaction, an Overman rearrangement reaction, a ring‐closing metathesis reaction, and an amination reaction. Late introduction of the furan ring during the synthesis of (?)‐nakadomarin A means that the key tetracyclic ketone derivative has the potential to serve as an advanced intermediate for the synthesis of related marine alkaloids.     

A new approach to highly substituted cyclopentanoids from a concise formal synthesis of (+)-roseophilin

A convergent reaction sequence involving a reductive coupling and a chiral Br?nsted acid catalyzed Nazarov reaction is utilized in a concise formal synthesis of (+)-roseophilin (11 steps via longest linear sequence, 10.2% yield, 95% ee).     

Steroide und Sexualhormone. 238. Mitteilung [1]. Die Synthese von 14βO, 18N-Ep (oxyäthanoimino)-Steroiden

The synthesis of the title compound 3 is described. The reaction sequence will serve as a model for a partial synthesis of batrachotoxinin A ( 2 ).     

Tandem Diels-Alder/fragmentation approach to the synthesis of eleutherobin

[reaction: see text] A synthesis of 28, the carbon framework of the eleutherobin aglycone, is reported in a 15-step sequence from readily available starting materials. The tandem Diels-Alder reaction of 6 and 7 to produce 18, in which three new rings and six new stereocenters are formed, is a key step in the reaction sequence.     

Oxidative cyclizations: the asymmetric synthesis of (-)-alliacol A

A tandem anodic coupling-Friedel-Crafts alkylation strategy has been used to rapidly complete the asymmetric synthesis of alliacol A. The anodic oxidation reaction allowed for the generation of a new bond between two nucleophiles. In the synthesis, the absolute stereochemistry of the final natural product is set relative to a methyl group that is incorporated early in the sequence using an asymmetric Michael reaction.     

Gram-scale synthesis of the A'B'-subunit of angelmicin B

A gram-scale enantiospecific synthesis of the A'B'-subunit of angelmicin B is reported. The synthesis involves a Lewis acid catalyzed contrasteric Diels-Alder reaction and a tandem silyl zincate 1,6-addition/enolate oxidation sequence.     

Total synthesis of (+)-aspidospermidine: a new strategy for the enantiospecific synthesis of aspidosperma alkaloids

A new strategy was developed for the enantiospecific synthesis of aspidosperma alkaloids. The key steps involve a novel ketene-lactonization reaction of a chiral vinyl sulfoxide to efficiently set up the quaternary carbon center, and a tandem Michael addition-alkylation reaction sequence to form the polycyclic core structure. This new strategy was employed in the total synthesis of natural product (+)-aspidospermidine.     

A diels-alder route to 7,8-disubstituted-1,2,3,4-tetrahydroisoquinolines

A novel synthesis of some difficultly accessible tetrahydroisoquinolines has been developed, utilizing a Diels-Alder reaction sequence.     

Development of a stepwise [3 + 3] annelation to functionalized piperidines

[reaction: see text] A stepwise formal [3 + 3] cycloaddition sequence via a Grignard addition-cyclization reaction leads to a much improved piperidine synthesis. This methodology provides improved flexibility in both the aziridine substrate and TMM equivalent.     

Total synthesis of cochleamycin A

[reaction: see text] Cochleamycin A (1) was synthesized in 2.4% overall yield via a 23-step linear sequence starting from 3-butene-1-ol. Key features of the synthesis include the synthesis of (Z)-1,3-diene 21 via a Stille coupling of 4 and 5 and a transannular Diels-Alder reaction of macrocycle 26 to provide the complete carbon skeleton of 1.     

Activated nitriles in heterocyclic synthesis. A novel synthesis of pyrazine derivatives

A novel synthesis of pyrazine derivatives from the reaction of α-tosyloximinonitriles with several active methylene enaminonitrile derivatives is reported. The reaction sequence is discussed.     

Tandem Allylboration–Prins Reaction for the Rapid Construction of Substituted Tetrahydropyrans: Application to the Total Synthesis of (−)‐Clavosolide A

Tetrahydropyrans are common motifs in natural products and have now been constructed with high stereocontrol through a three‐component allylboration‐Prins reaction sequence. This methodology has been applied to a concise (13 steps) and efficient (14 % overall yield) synthesis of the macrolide (?)‐clavosolide A. The synthesis also features an early stage glycosidation reaction to introduce the xylose moiety and a lithiation‐borylation reaction to attach the cyclopropyl‐containing side chain.     

Formal synthesis of (-)-apicularen A

[reaction: see text] A formal synthesis of (-)-apicularen A has been completed. The synthesis features a cyanohydrin acetonide coupling as a convergent approach to the C9-C18 segment and an intramolecular Diels-Alder addition sequence to create both the 10-membered macrocycle and the aromatic ring.     

Diastereoselective synthesis of the C(17)-C(28) fragment (the C-D spiroketal unit) of spongistatin 1 (altohyrtin A) via a kinetically controlled iodo-spiroketalization reaction

[reaction: see text] A convergent and stereocontrolled synthesis of spiroketal 15 corresponding to the C-D fragment of spongistatin 1 has been accomplished by a sequence utilizing a kinetically controlled intramolecular iodo-spiroketalization of glycal 2, which in turn was synthesized via a ring-closing metathesis reaction.     

Total synthesis of (-)-okilactomycin

A highly convergent synthesis of (-)-okilactomycin is described. Key reactions of this synthesis include a strategy-level diastereoselective oxy-Cope rearrangement/oxidation sequence, a Petasis-Ferrier union/rearrangement tactic, and an efficient RCM reaction to construct the 13-membered macrocyclic ring.     

Synthesis of fused imidazo azepine derivatives by sequential van Leusen/enyne metathesis reactions

A facile synthesis of fused imidazo azepine derivatives by a van Leusen/intramolecular enyne metathesis synthetic sequence is reported. The two-step reaction sequence generates compounds of significant molecular complexity from simple starting materials in an expedient fashion with good overall yields.     

Synthesis of fused triazolo-imidazole derivatives by sequential van Leusen/alkyne–azide cycloaddition reactions

A facile synthesis of fused triazolo imidazole derivatives by a van Leusen/alkyne–azide cycloaddition synthetic sequence is reported. The two-step reaction sequence generates compounds of significant molecular complexity from simple starting materials in an expedient fashion with good overall yields.     

Stereoselective synthesis of C-glycosides from carboxylic acids: the tandem Tebbe-Claisen approach

A variety of beta- or alpha-C-glycosides may be readily accessed in an entirely stereoselective fashion from esters derived from the reaction of carboxylic acids and 3-hydroxy glycals, by way of a tandem reaction sequence of Tebbe methylenation and Claisen rearrangement. Though of wide scope, for example allowing the synthesis of 1-6 linked C-disaccharides, the methodology does not currently allow the synthesis of C-glycosyl alpha-amino acids.     

Two successive one-pot reactions leading to the expeditious synthesis of (−)-centrolobine

A very short and efficient synthesis of (−)-centrolobine has been achieved by using two successive one-pot reactions. The first sequence involves a cross-metathesis reaction/hydrogenation/lactonization and the second sequence is a Grignard addition/reduction.