Spiro decane

Benzimidazoles with a hetero spiro-decane residue as NPY-Y5 antagonists. WO 2008129007, http // www.wipo.int/patentscope/search/en/ W02008129007 (to GlaxoSmithKline pic). 

Cyclohexanedione monoethylene acetal (l,4-dioxa-spiro[4.5]decan-8-one) [4746-97-8] M 156.2, m 70-73", 73.5-74.5". Recrystd from pet ether and sublimes slowly on attempted distillation. Also purified by dissolving in Et20 and adding pet ether (b 60-80°) until turbid and cool. [Gardner et al. J Am Chem Soc 22 1206 I957 Britten and Lockwood J Chem Soc Perkin Trans I 1824 1974.]... 

A mixture of 7.3 parts l-chloro-4,4-di-(4-fluorophenyl)-butane, 5.1 parts l-phenyl-4-oxo-l,3,8-triaza-spiro(4,5)-decane, 4 parts sodium carbonate, a few crystals of potassium iodide in 200 parts 4-methyl-2-pentanone is stirred and refluxed for 60 hours. After cooling the reaction mixture is treated with water. The organic layer is separated, dried, filtered and evaporated. The solid residue is recrystallized from 80 parts 4-methyl-2-pentanone, yielding l-phenyl-4-oxo-8-[4,4-di-(4-fluorophenyl)-] butyl-1,3,8-triaza-spiro(4,5)decane, melting point 187.5° to 190°C. 

The general features of the monensin synthesis conducted by Kishi et al. are outlined, in retrosynthetic format, in Scheme 1. It was decided to delay the construction of monensin s spiroketal substructure, the l,6-dioxaspiro[4.5]decane framework, to a very late stage in the synthesis (see Scheme 1). It seemed reasonable to expect that exposure of the keto triol resulting from the hydrogen-olysis of the C-5 benzyl ether in 2 to an acidic medium could, under equilibrating conditions, result in the formation of the spiroketal in 1. This proposition was based on the reasonable assumption that the configuration of the spiroketal carbon (C-9) in monensin corresponds to the thermodynamically most stable form, as is the case for most spiroketal-containing natural products.19 Spiro-ketals found in nature usually adopt conformations in which steric effects are minimized and anomeric effects are maximized. 

Spiro[4.5]decane-l,4-dione and Ethyl 4-Cyclohexyl-4-oxobutanoate... 

Mit einem groBeren Hydrid-OberschuB und bei langerer Reaktionsdauer liefert 1-Oxa-4-thia-spiro[4.5]decan 6 3 % A thy l-cycloh exyl-sulfan neben 20% 2-Cyclohexylthio-athanol... 

Similar reactions were carried out with 4//-tetrahydropyran-4-one, l-ethoxycarbonyl-4-piperidone, 4-alkylcyclohexanones, and 1,4-dioxa-spiro[4,5]decan-8-one to give the corresponding aminomethylenemalonates (278, X = O, NCOOEt, MeCH, EtCH, (CH,0),C) (86EUP168350 87USP4647566). 

Sattelkau and Eilbracht90 have exploited the Claisen rearrangement of allyl vinyl ethers in their synthesis of several spiro compounds. As shown below in equation 62, 7,9-dimethyl-l,4-dioxa-spiro[4,5]decan-8-one, 118, was converted to a ,/J-unsaturated ester 119 which was reduced to allyl alcohol 120906. Allyl vinyl ether 121 underwent a rhodium-catalyzed Claisen rearrangement to afford 7r,13r-dimethyl-l,4-dioxa-(8rC9)-dispiro[4.2.4.2]tetradecan-10-one (122) in 36% yield. 

SPIROANNELATION OF ENOL SILANES 2-OXO-5-METHOXYSPIRO[5.4]DECANE (Spiro[4.5]decan-1-one, 4-methoxy-)... 

Spiro(4,5)decane Spiro(5,5)undecane Spiro(5,6)- dodecane alone... 

Studies directed toward the synthesis of bicyclomycin have resulted in the discovery of efficient routes to the construction of the 2-oxa-8,10-diazabicyclo[4.2.2]decane system (160). Thus, the monolactim ether (155) with a hydroxypropyl side chain at position 3, on oxidation with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ), gave the product (156) in good yield, presumably via an iminium species (Scheme 51). No trace of the spiro compound (157) could be detected in this reaction. The formation of (156) is probably kinetically controlled. Prior protection of the alcohol as a silyl ether, followed by DDQ oxidation, gave the pyrazinone (158) subsequent deprotection and acid treatment gave the thermodynamically preferred spiro compound (159). The method has been extended to the synthesis of (160), having an exocyclic methylene this compound is a key intermediate in the total synthesis of bicyclomycin [88JCS(P1)2585]. 

Vetivanes are sesquiterpene ketones occuring in vetiver oil. Vetivane is basically a spiro[4,5]decane 99 (Structure 4.28). Although structurally different as in the case of a-vetivone 100 and /1-vetivone 101, they are characteristic compounds present in vetiver oil. Analogues such as a-vetispirene 102 and fi-veti-spirene 103 may occur as well. 

Cyclohexanedione monoethylene acetal (l,4-dioxa-spiro[4,5]decan-8-one) [4746-97-8]... 

Adam, G., Cesura, A., Kolczewski, S., Roever, S., Wichmann, J. (F. Hoffmann-La Roche AG) Di- or triaza-spiro(4,5)decane derivatives, EP963985 (1999c). 

Wichmann, J., Adam, G., ROver, S., Hennig, M., Scaione, M., Cesura, A.M., Dautzenberg, F.M., Jenck, F. Synthesis of (1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl) -1-phenyi-1,3,8-triaza-spiro[4.5]decan-4-one, a potent and selective orphanin FQ (OFQ) receptor agonists with anxiolytic-like properties, Eur. J. Med. Chem. 2000, 35, 839-851. 

Thioxo-6,7,9-triazaspiro[4.5]decan-10-one (714a) and 3-thioxo-l,2,4-triaza-spiro[5.5]undecan-5-one (714b) were obtained when the l-(l-thiosemicarbazido)cyclo-alkanecarboxamides (713) were treated with sodium ethoxide (63FRP1324339). 

These compounds range through monocyclic (with a bisabolane framework), bicyclic (with an eudesmane, amorphane, axane, guaiane, isodaucane, or gorgonane framework), tricyclic (with an aromadendrane, cubenane, maaliane, pupukeanane, or trachyopsane framework), and spiro[4,5]decane carbon skeletons. 

---