A Concise Asymmetric Synthesis of (2S,3S,7S)-3,7-Dimethylpentadecan-2-yl Acetate and Propionate, the Sex Pheromones of Pine Sawflies

Abstract

(2S,3S,7S)-3,7-Dimethylpentadecan-2-yl acetate (2) and its propionate analogue (3) are the main sex pheromones of all Neodiprion species and Diprion similes, respectively. Starting from (S)-malic acid and employing a highly chemo-, regio-, and stereoselective tandem ester reduction-epoxide formation-reductive epoxide-opening reaction protocol, an efficient total synthesis of (2S,3S,7S)-2 and -3 is reported herein.

Lewis Base–Brønsted Acid–Enzyme Catalysis in Enantioselective Multistep One‐Pot Syntheses

“…[1][2][3] In recent advances it was demonstrated how elegant advantages of the individual catalytic steps can be exploited without the need for extensive purification, long hands-on times or large amounts of solvents.S ometimes combined approaches even turn out to be superior to individual steps by providing higher overall yields or avoiding the direct handling of certain troublesome materials.N aturally,h owever,t hose potentially fruitful endeavors bear challenges in orchestrating as uitable arrangement of reagents,catalysts and conditions to prevent not only undesired side reactions or decomposition of compounds,but also especially the inactivation of catalysts. [4][5][6][7][8][9][10][11][12][13] Thefocus of the present study is on a-methylated ketones 1 [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] and diols 2, [32][33][34][35][36][37][38][39][40] which are used extensively in natural product syntheses.O ver decades,t hey not only proved indispensable for finding and examining new pharmacologically active agents,but also for elucidating the mode of action of established blockbusters ranking among the most important drugs by sale.…”

“…[4][5][6][7][8][9][10][11][12][13] Thefocus of the present study is on a-methylated ketones 1 [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] and diols 2, [32][33][34][35][36][37][38][39][40] which are used extensively in natural product syntheses.O ver decades,t hey not only proved indispensable for finding and examining new pharmacologically active agents,but also for elucidating the mode of action of established blockbusters ranking among the most important drugs by sale. [41,42] Well-established routes towards ketone 1 [16,31,43] and diols 2 [36,37,[44][45][46][47] apply stoichiometric amounts of reagents ...…”

Lewis‐Base‐Brønsted‐Säure‐Enzym‐Katalyse in enantioselektiven mehrstufigen Eintopf‐Synthesen

“…Natürlich sind diese potenziell vielversprechenden Bemühungen mit der Herausforderung verbunden, ein geeignetes Ensemble von Reagenzien, Katalysatoren und Bedingungen zu orchestrieren, um nicht nur unerwünschte Nebenreaktionen oder die Zersetzungen von Produkten, sondern insbesondere auch die Inaktivierung von Katalysatoren zu verhindern. [4][5][6][7][8][9][10][11][12][13] Im Fokus der vorliegenden Arbeit stehen a-methylierte Ketone 1 [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] und Diole 2, [32][33][34][35][36][37][38][39][40] die in Naturstoffsynthesen in großem Umfang eingesetzt werden. Sie erwiesen sich über Jahrzehnte nicht nur als unverzichtbar fürdie Suche nach und Untersuchung von neuen pharmakologisch aktiven Wirkstoffen, sondern auch fürd ie Aufklärung der Wirkungsweise etablierter Blockbuster,d ie zu den umsatzstärksten Medikamenten zählen.…”

“…Sie erwiesen sich über Jahrzehnte nicht nur als unverzichtbar fürdie Suche nach und Untersuchung von neuen pharmakologisch aktiven Wirkstoffen, sondern auch fürd ie Aufklärung der Wirkungsweise etablierter Blockbuster,d ie zu den umsatzstärksten Medikamenten zählen. [41,42] Etablierte Sequenzen zur Synthese des Ketons 1 [16,31,43] und der Diole 2 [36,37,[44][45][46][47] verwenden stçchiometrische Mengen an Reagenzien und enantiomerenreine Ausgangsmaterialien (Schema 1A-C). [48] Die Methoden wurden bis in die jüngste Vergangenheit jahrzehntelang eingesetzt und erwiesen sich als produktiv und geeignet fürdie Naturstoffsynthese.…”

Transformation of Esters into 2‐Substituted Allyl Halides via Tertiary Cyclopropanols: Application in the Stereoselective Synthesis of (2S,3S,7S)‐3,7‐Dimethyl‐2‐pentadecyl Acetate, the Sex Pheromone of the Pine Sawfly Neodiprion sertifer

“…The stereoselective synthesis of compound 1 and its acylates has been described in several papers 3–5. Alkylation reactions of chiral oxiranes, [3,4a,b,f] alkyl sulfonates, [4e,f,h] β‐hydroxy acid esters,4h derivatives of alkanoic acids with oxazoline or prolinol chiral auxiliaries,3,4c as well as Claisen rearrangement of allyl vinyl ethers4f have been used in the creation of chiral centres at the C‐3 and C‐7 positions of this molecule. Resolution of diastereomeric mixtures of α‐methyl‐substituted secondary alcohols by crystallization4d,4g and functional group manipulations of ( R )‐citronellic acid [4a,b,d,g] are other methods that have also been used to create chiral centres at the C‐3 and C‐7 positions, respectively.…”