Asymmetrische Synthese beider Enantiomere von (E)‐4,6‐Dimethyl‐6‐octen‐3‐on – Abwehrsubstanz der Weberknechte Leiobunum vittatum und L. calcar (Opiliones)

Abstract

Das acyclische Enon (E)-4,6-Dimethyl-6-octen-3-on (1) ist die Hauptkomponente des Abwehrsekrets der Weberknechte Leiobunum oittatum und L. calcar (Opiliones). Beide Enantiomere [(S)-1 und ( R ) -I ] sowie racemisches 1 werden bequern aus Diethylketon 2 und dem Bromid 3 unter Verwendung der Hydrazon-Methode synthetisiert. Durch LIS-NMR-Technik wird gezeigt, daB die acyclische Ketonalkylierung mit praktisch vollstandiger asymmetrischer Induktion erfolgt (ee 2 97%). Die allbekannten Weberknechte oder Kanker (Ordnung Opiliones), die wegen ihrer langen, stelzenartigen Beine im Volksmund auch als ,,Schneider, Geist, Keilhaken" etc., engl. ,,daddy longlegs", bezeichnet werden, gehoren zur Klasse der Spinnentiere (Arachnoidea). Bei feindlichen Attacken geben sie aus ihren zwei Abwehrdrusen ein Sekret ab und erzeugen hierbei einen starken Geruch'). In der Unterordnung Palpatores, Familie Phalangiidae, wurde bei Leiobunum vittatum ' ) (neben 4-Methyl-3-heptanon".')) und bei Leiobunum calcar 6, (neben 2,4-Dimethyl-2,4-hexadien-l-o17)) ein acyclisches Enon, die Titelsubstanz (E)-4,6-Dimethyl-6-octen-3-on (l), als wichtigster Bestandteil des Abwehrsekrets identifiziert. Die absolute Konfiguration des nur in wenigen Mikrolitern aus dem Abwehrsekret zuganglichen Enons 1 ist unbekannt. Die zwei bisher beschriebenen Synthesen von 1 sind nicht stereoselektiv und fuhren lediglich zum Racemat 3,8). Asymmetric Synthesis of Both Enantiomers of (E)-Wir berichten hier iiber eine einfache und effiziente Asymrnetrische Synthese beider Enantiomere [(S)-1 und (R)-1] dieses Abwehrstoffes unter Verwendung der HydrazonMethode'). Die retrosynthetische Analyse fuhrt direkt zu den einfachen Bausteinen Diethylketon (2) und dem aus Tiglinsaure leicht zuganglichen Brornid (E)-l-Brorn-2-methyl-2-buten lo) (3).

Asymmetric Syntheses Using the SAMP ‐/ RAMP ‐Hydrazone Method: ( S )‐(+)‐4‐Methyl‐3‐Heptanone

“…The title ketone (S)-4, which is 400 times more active than its enantiomer, 7,10 is the principal alarm pheromone of the leaf-cutting ant Atta texana. It has also been identified as an alarm pheromone in three other ant genera of the subfamily Myrmicinae, 7,11 as a component of the defensive secretion of the "daddy longlegs" Leiobunum vittatum (Opiliones), 12,13 and is produced by the elm bark beetles Scolytus scolytus (F.) and S. multistriatus. 14 The ketone (S)-4 and/or its enantiomer (R)-4 have been prepared via resolution of an intermediate, 10 starting from (R)-citronellic acid, 15 by stoichiometric asymmetric synthesis 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18 19 (76-88% ee), and by a microbiological method.…”

“…Because deprotonated SAMP-/RAMP-hydrazones react with nearly the entire palette of electrophiles, this new methodology, a chiral version of the now widely used dimethylhydrazone (DMH) method, 3 opens an elegant and economical entry to a great variety of important classes of compounds with good overall chemical yields and excellent diastereo-and enantioselectivities. The following stereoselective reactions may be mentioned: α-alkylations or aldehydes 8,26 and ketones; 5,6,8,13 diastereo-and enantioselective aldol reactions; 9,27,28 diastereo-and enantioselective Michael additions to form β,γ-substituted δ-keto esters, 29,30 δ-lactones, 31 and various heterocycles, such as dihydropyridines, octahydroquinolinediones and hexahydroquinolinones; 32 33 αalkylations of β-keto esters; 21,22,23,24,25 and, finally, asymmetric syntheses of α-and/or β-substituted primary amines 23,24 via alkylation-reductive amination of aldehydes and ketones 34 or nucleophilic addition to aldehyde-SAMP-/RAMP-hydrazones, followed by N-N bond cleavage. 35 This broad applicability is summarized in Figure 1, and typical examples are listed in Table I.…”

“…Using these conditions, the ozonolysis required at least 4 hr, rather than the 30 min suggested by the submitters. 13. Caution!…”

Efficient Stereoselective Total Synthesis of Denticulatins A and B

“…The other required fragment, ketone 5, was obtained from the ally1 alcohol 16"' by Claisen rearrangement to the acid 17 and subsequent reaction with ethyllithium (Scheme 3). The constitution and configuration of 5 were checked by comparison with a sample prepared according to Enders et al [3,8] The ketone 5 was converted with Hunig base/9BBN-OTf into the enol borinate 18. The (3-configuration of the enol double bond was verified by transformationtg1 of 18 into the corresponding silyl enol ether, which showed the characteristic C4 signal at 6 = 37.6 in the 13C-NMR spectrum.…”

Identification and Assignment of the Absolute Configuration of Biologically Active Methyl-Branched Ketones from Limnephilid Caddis Flies

“…[14] Although the enantiomers of leiobunone have been synthesized, the absolute configuration of the natural product is still unknown. [15] The branched ketones 4b and 4c were previously identified from the desert wasp Dasymutilla occidentalis, but again, the absolute configuration could not be determined. [16] The biological significance of all these compounds is unknown.…”