Total Synthesis,Stereochemical Assignment,and Field‐Testing of the Sex Pheromone of the Strepsipteran Xenos peckii

The sex pheromone of the endoparasitoid insect Xenos peckii (Strepsiptera: Xenidae) was recently identified as (7E,11E)‐3,5,9,11‐tetramethyl‐7,11‐tridecadienal. Herein we report the asymmetric synthesis of three candidate stereostructures for this pheromone using a synthetic strategy that relies on an sp³–sp² Suzuki–Miyaura coupling to construct the correctly configured C7‐alkene function. Comparison of ¹H NMR spectra derived from the candidate stereostructures to that of the natural sex pheromone indicated a relative configuration of (3R*,5S*,9R*). Chiral gas chromatographic (GC) analyses of these compounds supported an assignment of (3R,5S,9R) for the natural product. Furthermore, in a 16‐replicate field experiment, traps baited with the synthetic (3R,5S,9R)‐enantiomer alone or in combination with the (3S,5R,9S)‐enantiomer captured 23 and 18 X. peckii males, respectively (mean±SE: 1.4±0.33 and 1.1±0.39), whereas traps baited with the synthetic (3S,5R,9S)‐enantiomer or a solvent control yielded no captures of males. These strong field trapping data, in combination with spectroscopic and chiral GC data, unambiguously demonstrate that (3R,5S,9R,7E,11E)‐3,5,9,11‐tetramethyl‐7,11‐tridecadienal is the X. peckii sex pheromone.     

Asymmetric Total Synthesis of (‐)‐Octahydro‐1H‐benzofuro[3,2‐e]isoquinoline,A Partial Structure of Morphine

Octahydro‐1 H‐benzofuro[3,2‐e]isoquinolines, which possess the ACNO partial structure of morphine, displayed potent oral analgesic and narcotic‐antagonism activity. However, due to inefficiency in their synthesis the ACNO derivatives have not been developed for clinical use. Here, we report in detail the first asymmetric total synthesis of (‐)‐octahydro‐1 H‐benzofuro[3,2‐e]isoquinoline as exemplified by the preparation of (‐)‐ 1 and (‐)‐ 2 . The key intermediate (+)‐5‐hydroxy‐3,4,5,6,7,8‐hexahydro‐1 H‐isoquinoline‐2‐carboxylic acid ethyl ester ((+)‐ 5 ) was prepared in 81% yield and with 100% ee by asymmetric reduction of 5‐oxo‐3,4,5,6,7,8‐hexahydro‐1 H‐isoquinoline‐2‐carboxylic acid ethyl ester ( 6 ) using RuCl[(R,R)‐Tsdpen](p‐cymene) as catalyst with a S/C of 200. The three chiral centers of ACNO skeleton were constructed via a reaction sequence of asymmetric transfer hydrogenation, Heck reaction, and catalytical hydrogenation, and all of these stereoselective reactions were metal‐catalyzed (i.e. Ru, Pd, and Pt, respectively).     

Asymmetric Total Synthesis of (−)‐Kravanhin B

The first asymmetric total synthesis of kravanhin B has been accomplished with a linear reaction sequence of 13 steps starting from (R)‐(?)‐carvone. The synthesis features an intramolecular aldol cyclization to construct the desired cis‐fused decalin skeleton and an acid‐catalyzed dehydration and olefin isomerization to install the γ‐butenolide ring.     

Maculatic Acids—Sex Attractant Pheromone Components of Bald‐Faced Hornets

Yellowjackets in the genera Vespula and Dolichovespula are prevalent eusocial insects of great ecological and economic significance, but the chemical signals of their sexual communication systems have defied structural elucidation. Herein, we report the identification of sex attractant pheromone components of virgin bald‐faced hornet queens (Dolichovespula maculata). We analyzed body surface extracts of queens by coupled gas chromatographic–electroantennographic detection (GC‐EAD), isolated the compounds that elicited responses from male antennae by high‐performance liquid chromatography (HPLC), and identified these components by GC mass spectrometry (MS), HPLC‐MS, and NMR spectroscopy. In laboratory olfactometer experiments, synthetic (2Z,7E)‐3,7‐dimethyldeca‐2,7‐diendioic acid (termed here maculatic acid A) and (2Z,7E)‐10‐methoxy‐3,7‐dimethyldeca‐10‐oxo‐deca‐2,7‐dienoic acid (termed here maculatic acid C) in binary combination significantly attracted bald‐faced hornet males. These are the first sex attractant pheromone components identified in yellowjackets.     

An efficient asymmetric synthesis of (4R,8R)‐4,8‐dimethyldecanal,the most active component of natural Tribolure

An asymmetric synthesis of (4R,8R)‐4,8‐dimethyldecanal, the most active component of natural tribolure, was achieved through an asymmetric methylation as a key step and chiral‐pool strategy. Natural tribolure is a mixture of four stereoisomers, (4R,8R)/(4R,8S)/(4S,8R)/(4S,8S), and their ratio is 4/4/1/1. However, the (4R,8R)‐isomer is the most active one. Based on a chiral‐pool strategy, we used a recycled chiral molecular (R)‐4‐(Benzyloxy)‐3‐methylbutanal that we exploited in our previous article. After executing a C5 + C5 + C2 synthetic plan, the target molecule was obtained in nine linear steps and in 36.8% overall yield.     

Total synthesis of (3Z,9Z,6S,7R) and (3Z,9Z,6R,7S)-6,7-epoxy-3,9-octadecadienes

(3Z,9Z,6S,7R)-6,7-epoxy-3,9-octadecadiene (1) and (3Z,9Z,6R,7S)-6,7-epoxy-3,9-octadecadiene (2) have been stereoselectively synthesized in eight steps from 2-pentyn-1-ol with an overall yield of 8%. The key steps involved the Sharpless asymmetric dihydroxylation of (2E)-oct-2-en-5-yn-1-ol (6). The new synthetic method is suitable for multigram-scale preparation of 1 and 2 and might be used for producing sufficient quantities of the sex pheromone components for management of the pest of tea plantations.     

(5R,7R)-5-Methylheptadecan-7-ol: a novel sex pheromone component produced by a female lichen moth, Miltochrista calamina, in the family Arctiidae

A methyl-branched heptadecanol was found in the pheromone gland extract of a female lichen moth, Miltochrista calamina (Arctiidae, Lithosiinae). GC-MS analyses of the alcohol and a hydrocarbon derived from it by subsequent treatments with methanesulfonyl chloride and LiAlD₄ in microscale reactions indicated 5-methylheptadecan-7-ol (1) as one possible structure. The four stereoisomers of 1 in a ratio of 4:4:1:1 were prepared from (S)-β-citronellol with 60% ee, and were separated by a combination of achiral and chiral HPLC columns. The absolute configuration of each isomer was determined by the comparison with the chromatographic behaviors of other samples synthesized by a different scheme, which applied the Jacobsen hydrolytic kinetic resolution of racemic 1,2-epoxydodecane to fix the configuration of the 7-hydroxy group. Only the (5R,7R)-isomer attracted male moths; thus, we concluded that M. calamina females secrete (5R,7R)-1 as a sex pheromone, indicating a new chemical class of lepidopteran female sex pheromones.     

Synthesis of Murisolin, (15R, 16R, 19R, 20S)‐Murisolin A,and (15R, 16R, 19S, 20S)‐16,19‐cis‐Murisolin and Their Inhibitory Action with Bovine Heart Mitochondrial Complex I

The asymmetric total synthesis of murisolin, (15R, 16R, 19R, 20S)‐murisolin A, and (15R, 16R, 19S, 20S)‐16,19‐cis‐murisolin was performed by using an epoxy alcohol as a versatile chiral building block for synthesizing the stereoisomers of mono‐THF annonaceous acetogenins. The inhibitory activity of these murisolin compounds was examined with bovine heart mitochondrial complex I, and they showed almost the same activity.     

(-)-（3S, 6R）-3, 6-羟基-10-甲基十一酸及其三聚体的全合成

以廉价易得的异戊基溴为起始原料,以烯丙基二异松莰烷基硼烷参与的不对称烯丙基化反应和Yamaguchi酯化反应为关键步骤,实现了对(-)-(3S,6R)-3,6-二羟基-10-甲基十一酸(总收率27.5％)及其三聚体(总收率24.5％)的不对称全合成。     

Configurational Assignment of ‘Cryptochiral’ 10‐Hydroxystearic Acid Through an Asymmetric Catalytic Synthesis

An asymmetric catalytic total synthesis of (S)‐10‐hydroxystearic acid ( 1 ) for comparison of its absolute configuration to that of samples obtained by fermentative hydration of oleic acid is reported. The synthesis involves two catalytic key‐steps, namely Ru‐catalyzed anti‐Markovnikov hydration of 9‐decynoic acid ( 7 ) to 10‐oxodecanoic acid ( 5 ), followed by titanium‐mediated asymmetric catalytic addition of dioctylzinc ( 25 ) to 5 in presence of the chiral ligand N,N’‐((1R,2R)‐cyclohexane‐1,2‐diyl)bis(1,1,1‐trifluoromethanesulfonamide) ( 6 ). The synthesis is short and efficient and avoids use of protecting groups. Ozonolysis of 10‐undecynoic acid ( 9 ) to 5 provides an alternative entry point into the synthetic route. The double dehydrobromination of (ω,ω‐1)‐dibromoalkanoic acids to ω‐alkynoic acids under a variety of conditions was investigated with 10,11‐dibromoundecanoic acid ( 11 ) as model substrate and using qNMR to quantify all reaction products. The synthetic approaches presented here have the potential to be generalized to the asymmetric catalytic synthesis of a variety of n‐hydroxy‐fatty acids.     

Synthesis of Enantiomerically Pure Pheromones of South-Pacific Brown Algae: Hormosirene and Dictyopterene A

Hormosirene ((?)- 1 ; (1R,2R)-1-((1E,3Z)-1,3-hexadienyl)-2-vinylcyclopropane) is the specific sex attractant of several brown algae of the Australian shelf, while dictyopterene A ((+)- 2 ; (1R, 2R)-1-((1E)-1-hexenyl)-2-vinylcyclopropane) is found as a minor constituent of the pheromone bouquets. The asymmetric synthesis of the two hydrocarbons is performed by resolution of the amides (?)- 5 and (+)- 5a obtained from (?)-(R)-2-phenylglycinol and racemic trans-vinylcyclopropanecarboxylic acid (rac- 4 ) on silica gel. Both diastereoisomers are obtained optically pure. They are converted by stereoselective Wittig olefination into the title compounds. Compound (?)- 1 is the active mating pheromone of the reproductive system of the seaweed Xiphophora chondrophylla as established by biological-activity assays.     

Studies on the identification and syntheses of insect pheromones: XX. Synthesis of (7R, 8S)-(+)-sex pheromone of gypsy moth through the kinetic resolution of (±) allylic alcohol by Sharpless asymmetric epoxidation

The chiral epoxy alcohol 3 was synthesized in 92% e.e through the kinetic resolution of (±)-l-tridecen-3-ol 2 by Sharpless asymmetric epoxidation. 3 was then transformed to (7R, 8S)-1a, the sex pheromone of gypsy moth, in an overall yield of 60% in 5 steps.     

Enantioselective Allylation of (2E,4E)‐2,4‐Dimethylhexadienal: Synthesis of (5R,6S)‐(+)‐Pteroenone

Allylation, trans‐ and cis‐crotylation of (2E,4E)‐2,4‐dimethylhexadienal, a representative α,β,γ,δ‐unsaturated aldehyde, was carried out under different catalytic and stoichiometric conditions. The reactions catalyzed by organocatalysts TRIP‐PA and N,N′‐dioxides gave the best results with respect to yields, asymmetric induction, and catalyst load in comparison to other procedures. The developed methodology was applied in the enantioselective synthesis of (5R,6S)‐(+)‐pteroenone, a defensive metabolite (ichthyodeterrent) of the Antarctic pteropod Clione antarctica.     

Asymmetric Synthesis of All Possible Stereomers of 4‐Aminoglutamic Acid via Michael Condensation of Chiral Ni(II) Complexes of Glycine and Dehydroalanine

A new method for asymmetric synthesis of all possible stereomers of 4‐aminoglutamic acid has been developed. The method is based on asymmetric Michael condensation of the nucleophilic moiety of glycine and electrophilic moiety of dehydroalanine in their chiral Ni(II) complexes of the Schiff's bases with (S)‐ and (R)‐2‐N‐(N′‐benzylprolyl)aminobenzophenones, resulting in the formation of dimeric complexes of 4‐aminoglutamic acid. Stereoselectivity of the asymmetric condensation of the complexes exceeded 94%. The condensation of nucleophilic and electrophilic complexes in four possible combinations has resulted in the formation of dimeric complexes of all the stereomers of 4‐aminoglutamic acid: (2S,4S), (2S,4R)‐meso and (2R,4R). Optically active stereomers of 4‐aminoglutamic acid with high optical purity were isolated after decomposition of the dimeric complexes.     

Synthesis of (−)-(5R,6S)-6-acetoxyhexadecanolide based on l-proline-catalyzed asymmetric aldol reactions

A convenient method for proline-catalyzed asymmetric aldol reactions using synthons of straight-chain aliphatic aldehydes, and aldehydes bearing a 1,3-dithiane moiety at the β-position, has been developed. This method was successfully applied to the synthesis of (−)-(5R,6S)-6-acetoxyhexadecanolide, an oviposition attractant pheromone of the female Culex mosquito.     

Catalytic Asymmetric Total Synthesis of (−)‐Galanthamine and (−)‐Lycoramine

The catalytic asymmetric total syntheses of (?)‐galanthamine ( 1 ) and (?)‐lycoramine ( 2 ) have been achieved by using a conceptually new strategy featuring two metal‐catalyzed reactions as the key steps. A new method for the construction of 3,4‐fused benzofurans has been developed through a palladium‐catalyzed intramolecular Larock annulation reaction, which was successfully applied to the construction of the ABD tricyclic skeleton of 1 and 2 . To achieve the asymmetric synthesis of 1 and 2 , a Sc^III/N,N′‐dioxide complex was used to catalyze the enantioselective conjugate addition of 3‐alkyl‐substituted benzofuranone to methyl vinyl ketone for the construction of a chiral quaternary carbon center.     

Stereoselective synthesis of (2S,3S,7S)-3,7-dimethylpentadecan-2-ol and its propionate,the sex pheromones of pine sawflies

The stereoselective synthesis of (2S,3S,7S)-3,7-dimethylpentadecan-2-ol (diprionol) and its propionate, the sex pheromones of pine sawflies (Neodiprion sp. and other), in high enantiomeric purity was achieved from (1R,3S)-2,2-dichloro-3-methylcyclopropanecarboxylic acid. The carbon skeleton of diprionol was formed via copper-catalyzed cross-coupling reactions and diastereoselective methylation of the intermediate chiral α-methylbranched aldehyde with MeTi(Oi-Pr)₃ in the presence of [(R,R)-TADDOL]Ti(Oi-Pr)₂. The latter transformation leads to a syn-adduct with high stereoselectivity, which depends on the presence and configuration of the α-stereogenic center in the aldehyde. The diastereomeric purity of (2S,3S,7S)-diprionol can be substantially increased via crystallization of its 3,5-dinitrobenzoate.     

Enantioselective Entry to the Homalium Alkaloid Hoprominol: Synthesis of an (R,R,R)‐Hoprominol Derivative

The diastereoselective synthesis of the N‐ and O‐protected hoprominol derivative (R,R,R)‐ 6 is described. The building up of the bicyclic O‐silylated and di(N‐tosylated) asymmetric scaffold 6 succeeded by convergent preparation of the two basic chiral azalactam units 7a and 7b and their subsequent iterative linking by a known method (Scheme 5). Both 4‐alkyl‐hexahydro‐1,5‐diazocin‐2(1H)‐ones 7a and 7b were prepared from the chiral β‐amino acid portions 10a and 10b , respectively, by application of a set of reactions (e.g., N‐alkylation of 10a , b and Sb(OEt)₃‐assisted cyclization of the resulting open‐chain intermediates) already known. In comparison with the total syntheses of homaline ( 1 ) and homoprine ( 2 ), the newness of the described synthesis lies in the asymmetric approach to the difunctionalized fatty acid derivative 10b starting from (?)‐(S)‐malic acid ( 9 ) (Schemes 3 and 4). Key step in the preparation of 10b was the diastereoselective amination of the optically pure α,β‐unsaturated δ‐hydroxy homoallylic ester 14 via conjugate intramolecular aza‐Michael cyclization of the acylic δ‐(carbamoyloxy) intermediate 11 .     

Methyl (3R,5R)-3,5-dihydroxydecanoate in the asymmetric synthesis of Idea Leuconoe pheromone and formal syntheses of (+)-(3R,5R)-3-hydroxydecano-5-lactone, verbalactone, and Tolypothrix pentaether

A simple and efficient asymmetric synthesis of (5S,7R)-7-hydroxydodecano-5-lactone, a component of the giant danaine butterfly Idea leuconoe pheromone, and formal syntheses of (+)-(3R,5R)-3-hydroxydecano-5-lactone, verbalactone, and Tolypothrix pentaether have been accomplished starting from methyl (3R,5R)-3,5-dihydroxydecanoate. The latter is obtained from methyl 3-[(tributylstannyl)methyl]but-3-enoate using Keck allylation in the key step of the construction of its carbon skeleton.     

Ready access to the 6,8-dioxabicyclo[3.2.1]octane ring system using asymmetric heterocycloaddition induced by a chiral sulfoxide: application to the total synthesis of the Mus musculus pheromone

A new stereocontrolled total synthesis of the (1R,5S,7R)-exo-6,8-dioxabicyclo[3.2.1]oct-3-ene skeleton of the Mus musculus pheromone has been achieved via an asymmetric intermolecular Diels–Alder reaction and an intramolecular conjugated addition, controlled by a chiral auxiliary.