147363-82-4Relevant articles and documents
3,3-Dimethoxypropylsulfonyl Group: A new versatile protecting and activating group for amine synthesis
Sakamoto, Izumi,Iwaoka, Kazuya,Kawada, Yuta,Naito, Takanori,Makida, Kazuyoshi,Takeuchi, Yuki,Nishii, Takeshi,Horikawa, Mitsuyo,Kaku, Hiroto,Tsunoda, Tetsuto
, p. 3052 - 3060 (2018/05/23)
3,3-Dimethoxypropylsulfonyl (Dimps) chloride was prepared and used as a new versatile sulfonating agent for ammonia, primary and secondary amines to afford corresponding Dimps-amides in excellent yields. The resulting N-nonsubstituted and N-monosubstituted Dimps-amides, activated amines, were alkylated satisfactorily under new Mitsunobu conditions. The Dimps group was removed by treatment in aqueous solution under acidic followed by basic conditions. Furthermore, epilachnene, the defensive droplets from the Mexican bean beetle, Epilachna varivestis, was synthesized utilizing this Dimps methodology in short steps.
Efficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: Applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A
Wang, Chenbo,Yu, Miao,Kyle, Andrew F.,Jakubec, Pavol,Dixon, Darren J.,Schrock, Richard R.,Hoveyda, Amir H.
supporting information, p. 2726 - 2740 (2013/04/10)
The first broadly applicable set of protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed with 1.2-7.5 mol % of a Mo- or W-based monoaryloxide pyrrolide (MAP) complex at 22 °C and proceed to complete conversion typically within two hours. Utility is demonstrated by synthesis of representative macrocyclic alkenes, such as natural products yuzu lactone (13-membered ring: 73 % Z) epilachnene (15-membered ring: 91 % Z), ambrettolide (17-membered ring: 91 % Z), an advanced precursor to epothilones C and A (16-membered ring: up to 97 % Z), and nakadomarin A (15-membered ring: up to 97 % Z). We show that catalytic Z-selective cyclizations can be performed efficiently on gram-scale with complex molecule starting materials and catalysts that can be handled in air. We elucidate several critical principles of the catalytic protocol: 1) The complementary nature of the Mo catalysts, which deliver high activity but can be more prone towards engendering post-RCM stereoisomerization, versus W variants, which furnish lower activity but are less inclined to cause loss of kinetic Z selectivity. 2) Reaction time is critical to retaining kinetic Z selectivity not only with MAP species but with the widely used Mo bis(hexafluoro-tert-butoxide) complex as well. 3) Polycyclic structures can be accessed without significant isomerization at the existing Z alkenes within the molecule.
Z-SELECTIVE RING-CLOSING METATHESIS REACTIONS
-
Page/Page column 161-163; 170-171; 174-175, (2013/02/28)
The present invention relates generally to olefin metathesis. In some embodiments, the present invention provides methods for Z-selective ring-closing metathesis.
A modified thermodynamically controlled deracemization of 2-allylcyclohexanone and its application to asymmetric synthesis of (R)-(-)-epilachnene
Kaku, Hiroto,Okamoto, Natsuko,Nakamaru, Aya,Tsunoda, Tetsuto
, p. 516 - 517 (2007/10/03)
The efficiency of thermodynamically controlled deracemization was influenced considerably by the solvent used. Based on this finding, an improved method was developed, by which 2-allylcyclohexanone was converted to the R-isomer of 93% ee in 72% yield. As an application of the method, (R)-(-)-epilachnene, an antipode of the defensive droplets from the Mexican bean beetle, Epilachna varivestis, was synthesized in short steps.
Synthesis of macrocyclic insect-derived alkaloids
Farmer, Jay J.,Schroeder, Frank C.,Meinwald, Jerrold
, p. 2594 - 2606 (2007/10/03)
Macrocyclic lactonic alkaloids found in the pupal secretions of two species of a coccinellid beetle (genus Epilachna) were prepared in enantiomerically pure form via an efficient synthetic route using enantiomerically pure α-amino acids as chiral-pool starting materials. Macrocycles with rings containing up to 98 atoms were synthesized in good yield using Mukaiyama's macrolactonization conditions.
An improved and novel approach to macrolactonisation using di-tert-butyl dicarbonate
Nagarajan,Satish Kumar,Venkateswara Rao
, p. 12349 - 12360 (2007/10/03)
A new, facile, mild and simple method for the synthesis of macrolides was achieved from ω- hydroxy acids using di-tertbutyl dicarbonate (Boc2O), a cheap and commercially available reagent. A wide range of substrates were tested and give good yield of lactones. The effect of various simple bases on the yield of the macrolactonisation reaction was also studied.
Ring closing alkyne metathesis. Comparative investigation of two different catalyst systems and application to the stereoselective synthesis of olfactory lactones, azamacrolides, and the macrocyclic perimeter of the marine alkaloid nakadomarin A
Fürstner, Alois,Guth, Oliver,Rumbo, Antonio,Seidel, Günter
, p. 11108 - 11113 (2007/10/03)
Previously unknown ring closing metathesis reactions of diynes are described which open an efficient and stereoselective entry into macrocyclic (Z)-alkenes if the resulting cycloalkyne products are subjected to Lindlar reduction. This new two-step strategy offers significant advantages in stereochemical terms over conventional RCM of dienes which usually leads to (E,Z)-mixtures when applied to the formation of large rings. The tungsten alkylidyne complex (tBuO)3W≡CCMe3 (1a) and analogues thereof as well as a structurally unknown species formed in situ from Mo(CO)6 and p-chlorophenol effect the crucial alkyne metathesis reactions in a highly efficient manner, with the former catalyst being more tolerant toward structural variations of the substrates and polar functional groups. Applications to the stereoselective synthesis of the olfactory compounds ambrettolide 23 and yuzu lactone 24, the insect repellent azamacrolides epilachnene 31 and homoepilachnene 33, as well as to the fully functional building block 64 required for a total synthesis of the cytotoxic alkaloid nakadomarin A 51 highlight the relevance of this new concept for natural product chemistry. In the latter case, the diyne substrate 62 necessary for ring closing alkyne metathesis was obtained via a novel furan synthesis relying on a palladium-catalyzed opening of a vinyl epoxide followed by an oxidative cyclization of the heterocyclic ring.
Synthesis of functionalized macrocycles by ring closing metathesis
-
, (2008/06/13)
The invention concerns an improved process for the preparation of macrocyclic products with 12 or more ring atoms containing one or more polar functional groups on the ring and/or one or more heteroatoms within the ring by ring closing metathesis (RCM) of suitably substituted diene precursors even if the substrates are devoid of any kind of conformational preorganization. Metal carbene complexes of Ru, Mo, W, Re, Os, which are tolerant towards the respective functional group and can either be isolated or prepared in situ are used as catalysts or catalyst precursors. Preferred catalysts or catalyst precursors are ruthenium complexes of the general type XX1 LL1 Ru=CRR1, wherein X, X1 =halogen, L, L1 =trialkylphosphine, R, R1=H, Ph, CH=CPh2 denote the most preferred embodiment. The process can be applied to the synthesis of olfactory compounds, perfumary ingredients, pheromones, crown ethers, antibiotics and pharmaceuticals for human and veterinary medicine.
Absolute configuration of insect-produced epilachnene
Farmer, Jay J.,Attygalle, Athula B.,Smedley, Scott R.,Eisner, Thomas,Meinwald, Jerrold
, p. 2787 - 2790 (2007/10/03)
Samples of (X) and (S)-epilachnene [(5Z)-11-propyl-12-azacyclotetradec-5-en olide] were synthesized from (R) and (S)-norvaline. The diastereomeric α-methoxy-α-trifluoromethylphenylacetyl amides of these synthetic samples, prepared using (S) α-methoxy-α-trifluoromethylphenylacetyl chloride, were well resolved by gas chromatography. Analogous derivatization and gas chromatographic analysis of a sample of epilachnene from the pupal secretion of the coccinellid beetle, Epilachna varivestis, established that the natural product is (S)-epilachnene.
Macrocycles by ring-closing metathesis
Fürstner, Alois,Langemann, Klaus
, p. 792 - 803 (2007/10/03)
The ruthenium carbene complexes 1 and 2 (0.05-5 mol %) catalyse highly efficient macrocyclization reactions of 1,ω-dienes by ring-closing metathesis (RCM). Key parameters for successful RCM are (i) the presence of a functional group which serves as a relay entity that assembles the reacting sites, (ii) an appropriate distance between this polar group and the alkenes to be metathesized, and (iii) low steric congestion near the double bonds. Contrary to previous assumptions, however, the ring size formed and the conformational predisposition of the substrates for ring closure turned out to be of minor importance. These aspects are illustrated by some straightforward syntheses of macrocyclic lactones, lactams, ethers and ketones, including the musk odored perfume ingredients Exaltolide, Exaltone and Arova 16, of the macrolide recifeiolide (24), as well as of the alkaloids epilachnene (40) and its homologue 9-propyl-10-azacyclododecan-12-olide (39), which are active principles of the defense secretions of the pupae of the mexican beetle Epilachnar varivestis.
