Final‐Stage Site‐Selective Acylation for the Total Syntheses of Multifidosides A–C

The first total syntheses of multifidosides A–C have been achieved. The synthetic strategy is characterized by catalytic site‐selective acylation of unprotected glycoside precursors in the final stage of the synthesis. High functional‐group tolerance of the site‐selective acylation, promoted by an organocatalyst, enabled the conventionally difficult molecular transformation in a predictable and reliable manner. An advantage of this strategy is to avoid the risks of undesired side reactions during the removal of the protecting groups at the final stage of the total synthesis.     

Synthesis of Cyclic Alkenyl Triflates by a Cationic Cyclization Reaction and its Application in Biomimetic Polycyclizations and Synthesis of Terpenes

Cyclic alkenyl triflates are useful intermediates in organic synthesis usually synthesized from ketones through a reaction involving enolization and trapping with a triflating agent. This sequence suffers from some stereochemical drawbacks owing to the basic conditions required. Herein, we describe a new acid‐mediated cationic cyclization reaction of enyne derivatives (or alkynols) to access cyclic alkenyl triflates. This new atom‐economical process is high yielding, scalable, technically very simple, proceeds without the need of any metallic reagent or catalyst, and more importantly, it complements and challenges conventional methodologies. We have also developed new biomimetic cationic cyclization reactions to yield interesting polycyclic compounds. As a demonstration of the potential of this method in the context of total synthesis, we have synthesized two terpenes: austrodoral and pallescensin A. Using the cationic cyclization in the key step of the synthetic routes allowed the synthesis of these natural products in a very simple, concise, scalable, and efficient way.     

The Photo‐Nazarov Reaction: Scope and Application

The reaction conditions and scope of the photo‐Nazarov reaction of aryl vinyl ketones were investigated. In contrast to the conventional acid‐catalyzed methods, this photolytic electrocyclization proceeds in the neutral or basic conditions. Irradiating substrates bearing various aromatic rings, acid‐sensitive groups, cyclohexenyl, cycloheptenyl, and unsaturated pyran with UV‐light (254 nm) smoothly yielded hexahydrofluorenones and related structures. This photo‐Nazarov reaction could also be applicable to the substrates carrying β‐alkyl groups on the enone, which gave corresponding polycyclic rings containing quaternary centers. These photo‐electrocyclized products may prove useful for synthesizing a variety of natural products and their derivatives. Further application of this mild photo‐Nazarov reaction in the synthesis of taiwaniaquinol B was achieved.     

Structure-Pattern-Based Total Synthesis

In this article the concept of structure-pattern-recognition and its application to total synthesis is summarized. By applying this synthetic strategy to the two biogenetically unrelated natural product families Sarpagine and Stemona alkaloids, a drastic increase of synthetic efficiency could be achieved. To highlight its potential, this strategy is compared with some elegant target-oriented syntheses. The importance of strategic planning and synthesis design is clearly demonstrated.     

A Formal Total Synthesis of Taxol Aided by an Automated Synthesizer

A 36‐step synthesis was carried out in automated synthesizers to provide a synthetic key intermediate of taxol. A key step involved a microwave‐assisted alkylation reaction to construct the ABC ring system from an AC precursor. Subsequent formation of the D ring afforded baccatin III, a well‐known precursor of taxol.     

Synthesis of the Bicyclic Lactone Core of Leonuketal,Enabled by a Telescoped Diels–Alder Reaction Sequence

The Diels–Alder cycloaddition reaction has become established as a fundamental approach for the preparation of complex natural products; however, successful application of the intermolecular Diels–Alder cycloaddition reaction to the synthesis of particularly congested scaffolds remains surprisingly problematic. Inspired by the terpenoid spiroketal natural product leonuketal, a challenging telescoped reaction sequence has been realized to access the core [2.2.2]‐bicyclic lactone ring system and its [3.2.1] isomer. Our four‐step, protecting‐group‐free process required detailed investigation to circumvent the problems of adduct fragmentation and intermediate instability. Successful solution of these practical issues, along with unambiguous structural determination of the target structures, provide useful insights that will facilitate future applications of the Diels–Alder cycloaddition reaction to challenging, highly congested molecular scaffolds and ongoing synthetic efforts towards this natural product.     

Catalytic Asymmetric Synthesis of Allylic Alcohols and Derivatives and their Applications in Organic Synthesis

Allylic alcohols represent an important and highly versatile class of chiral building blocks for organic synthesis. This Review summarizes the plethora of methods developed for the catalytic asymmetric synthesis of enantioenriched allylic alcohols. These include: dynamic kinetic resolution (DKR/DKAT), nucleophilic 1,2‐addition to carbonyl groups, allylic substitution, oxidation of C? H bonds, the addition of O nucleophiles to π systems, reduction of unsaturated carbonyl compounds, and an alternative route from enantioenriched propargylic alcohols. Furthermore, these catalytic asymmetric processes are exemplified by their applications in the syntheses of complex molecules such as natural products and potential therapeutic agents.     

Cascade Claisen Rearrangement: Rapid Synthesis of Polysubstituted Salicylaldehydes and Total Syntheses of Hemigossypol and Gossypol

A cascade Claisen rearrangement of a well‐organized maltol propargyl ether for the construction of polysubstituted salicylaldehydes is reported. This reaction features high atom economy (100 %), as well as catalyst‐free and gram‐scale conditions. Based on this novel methodology, the total synthesis of hemigossypol, gossypol, and their analogues has been realized.     

Synthesis of Rhodomyrtone Analogs Modified at C7

We developed a route to rhodomyrtone analogs that feature different acyl groups at C7. Since electrophilic substitution reactions on the aryl part of the rhodomyrtone core led to C5 derivatives, the C5 position was blocked by a chlorine. Subsequent Duff type formylation followed by Grignard addition to the aldehyde group and oxidation gave various phenones. The benzyl protecting groups were removed by hydrogenation or boron tribromide. Some derivatives turned out to be quite active against multiple resistant Staphylococcus aureus strains and a rhodomyrtone resistant mutant (Rom^R). The chlorine at C5 seems to have a beneficial effect on the antibacterial activity.     

Identification and Synthesis of Macrolide Pheromones of the Grain Beetle Oryzaephilus Surinamensis and the Frog Spinomantis Aglavei

Macrolide lactones, the so called cucujolides derived from unsaturated fatty acids, are aggregation pheromones of cucujid grain beetles. Thirty years ago, Oehlschlarger et al. showed that (3Z,6Z)‐dodeca‐3,6‐dien‐11‐olide ( 4 ) and the respective 12‐olide ( 7 ) attract the sawtoothed grain beetle Oryzaephilus surinamensis, whereas (5Z,8Z,13R)‐tetradeca‐5,8‐dien‐13‐olide ( 5 ) increases the response synergistically. The frass of this beetle is attractive for its parasitoid Cephalonomia tarsalis, which potentially can be used for pest control. A GC/MS analysis of attractive frass showed the presence of 5 , together with an unknown isomer. Cucujolide V was tentatively identified also in the femoral glands, pheromone‐releasing structures, of the Madagascan mantelline frog Spinomantis aglavei. Therefore, a new route to synthesize doubly unsaturated macrolides allowing the flexible attachment of the side chain was developed. A straightforward method to obtain Z configured macrolides involves ring‐closing alkyne metathesis (RCAM) followed by Lindlar‐catalyzed hydrogenation. This methodology was extended to homoconjugated diene macrolides by using RCAM after introduction of one Z configured double bond in the precursor by Wittig reaction. A tungsten benzylidyne complex was used as the catalyst in the RCAM reaction, which afforded the products in high yield at room temperature. With the synthetic material at hand, the unknown isomer was identified as the new natural product (5Z,8Z,12R)‐tetradeca‐5,8‐dien‐12‐olide, cucujolide X ( 8 ). Furthermore, the route also allowed the synthesis of cucujolide V in good yield. The natural products were identified by the synthesis of enantiomerically pure or enriched material and gas chromatography on chiral phases. The new macrolide (R)‐ 8 proved to be biologically active, attracting female O. surinamensis, but no males. The synthetic material allowed the identification of (R)‐ 5 in both the beetle and the frog.     

Atomic and bond properties in functionalized esters and amides

The properties of various atomic groups of molecules containing a carbonyl unit (XCOY) consisting of an ester (Y=OR) or amide function (Y=NHR) in different molecular environments (X=H, Me, Et, OH, OMe, NH₂, NHMe, F, Cl), as well as their influence on the properties of the alkyl chain (R=C₈H₁₇) in the molecule, were analyzed by use of the theory of atoms in molecules (AIM). To this end, the main atomic and bond properties for each atom in 18 carbonyl compounds of the aforementioned types were determined on the basis of 6-31++G**//6-31G* wave functions. The properties of the C and O atoms in the carbonyl group, and those of their bonds, are directly related to the nature and electronegativity of the X substituent and to the character of the Y group. The nature of the C Y bond and the properties of the Y group are also dependent on the proximity of the X group. Based on the precision with which integrated properties were determined, assessed by L(Ω), the properties of the methylene groups of the R chain located in α and β with respect to Y are essentially dependent on the nature of Y and, to a lesser extent, on that of X. The methylene group in γ with respect to Y exhibits a dependence on the nature of the latter that vanishes in more distinct groups; therefore, the methylene in ε can be assimilated to one in an alkane. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1444–1454, 1999