26532-22-9

Usage

Synthesis Reference(s)

The Journal of Organic Chemistry, 40, p. 2013, 1975 DOI: 10.1021/jo00901a039

InChI:InChI=1/C10H18O/c1-8(2)9-4-5-10(9,3)6-7-11/h9,11H,1,4-7H2,2-3H3/t9-,10+/m0/s1

Upstream product

• 20763-19-3 (methoxymethylene)triphenylphosphorane 
• 55659-40-0 (1R,2S)-grandisyl acetate 
• 68225-43-4 (1R,2S)-2-isopropenyl-1-methylcyclobutaneacetic acid 
• 136232-58-1 (1R,2R)-1-ethenyl-2-(1-hydroxy-1-methylethyl)-1-methylcyclobutane 
• 68225-41-2 (1R,2S)-2-acetyl-1-methylcyclobutaneacetic acid 
• 13170-43-9 (trimethylsilyl)methylmagnesium chloride 
• 131682-96-7 (1R,6R)-(-)-2,2,6-trimethyl-3-oxabicyclo<4.2.0>octane 
• 135253-40-6 tert-Butyl-[2-((1R,2S)-2-isopropenyl-1-methyl-cyclobutyl)-ethoxy]-diphenyl-silane 
• 63623-52-9 (1R,2S)-2-isopropenyl-1-methylcyclobutaneacetaldehyde 
• 83709-61-9 (+)-(1R,2R)-1-(2'-hydroxyethyl)-2-(1'-hydroxy-1'-methylethyl)-1-methylcyclobutane 
• 153610-32-3 (-)-(1R,4S,5S)-5-methyl-4-pivaloyloxymethyl-3-oxabicyclo<3.2.0>heptan-2-one 
• 157327-68-9 (-)-(1R,5S,6S)-5-hydroxy-2,2,6-trimethyl-3-oxabicyclo<4.2.0>octane 
• 153610-33-4 (-)-(1S,2R,1'S)-1-1',2'-dihydroxyethyl-2-1-hydroxy-1-methylethyl-1-methylcyclobutane 
• 157327-70-3 (-)-(1R,5S,6S)-5-O-thiocarbonylimidazolyl-2,2,6-trimethyl-3-oxabicyclo<4.2.0>octane 

Downstream Products

• 1229005-33-7 (1R,2S,6R)-2-hydroxymethyl-2,6-dimethyl-3-oxabicyclo[4.2.0]octane 
• 55659-40-0 (1R,2S)-grandisyl acetate 

Relevant academic research and scientific papers

Highly efficient approach to (+)-grandisol via a diastereoselective [2+2] photocycloaddtion 2(5H)-furanones

A new approach to (+) and (-)-grandisol is described through a diastereoselective photocycloaddition of ethylene to an easily available homochiral butenolide. Optically pure intermediates are obtained.

Catalytic enantioselective synthesis of benzocyclobutenols and cyclobutanolsviaa sequential reduction/C-H functionalization

We report here a sequential enantioselective reduction/C-H functionalization to install contiguous stereogenic carbon centers of benzocyclobutenols and cyclobutanols. This strategy features a practical enantioselective reduction of a ketone and a diastereospecific iridium-catalyzed C-H silylation. Further transformations have been explored, including controllable regioselective ring-opening reactions. In addition, this strategy has been utilized for the synthesis of three natural products, phyllostoxin (proposed structure), grandisol and fragranol.

Ring-Expansion Induced 1,2-Metalate Rearrangements: Highly Diastereoselective Synthesis of Cyclobutyl Boronic Esters

The broad synthetic utility of organoboron compounds stems from their ready ability to undergo 1,2-migrations. Normally, such shifts are induced by α-leaving groups or by reactions of alkenyl boronates with electrophiles. Herein, we present a new strategy to induce 1,2-metalate rearrangements, via ring expansion of vinylcyclopropyl boronate complexes activated by electrophiles. This leads to a cyclopropane-stabilized carbocation, which triggers ring expansion and concomitant 1,2-metalate rearrangement. This novel process delivers medicinally relevant 1,2-substituted cyclobutyl boronic esters with high levels of diastereoselectivity. A wide range of organolithiums and Grignard reagents, electrophiles, and vinylcyclopropyl boronic esters can be used. The methodology was applied to a short, stereoselective synthesis of (±)-grandisol. Computational studies indicate that the reaction proceeds via a nonclassical carbocation followed by anti-1,2-migration.

AN IMPROVED PROCESS FOR THE PREPARATION OF TIPIRACIL HYDROCHLORIDE AND INTERMEDIATES THEREOF

The present invention provides a process for the preparation of Tipiracil HCl of Formula (I) and intermediate thereof with improved yields and purities.

Ring-Closing Strategy Utilizing Nitrile α-Anions: Chiral Synthesis of (+)-Norchrysanthemic Acid and Expeditious Asymmetric Total Synthesis of (+)-Grandisol

Chiral syntheses of two distinct small cycloalkanes, (1R,3R)-(1Z)-norchrysanthemic acid and (+)-grandisol, were performed by characteristic ring-closing methodologies using carbanions at the α-position of nitriles (nitrile α-anions). (i) (1R,3R)-(1Z)-Norchrysanthemic acid, a highly potent ingredient of synthetic pyrethroid containing a cyclopropane structure, was synthesized from readily available (S)-epoxide derived from 3-methyl-but-2-en-1-ol in 7 steps in 23 % overall yield and with > 98 % ee. This sequence involves a trans-selective cyclopropane formation using the nitrile α-anion of (S)-3-mesyloxynitrile as the key step. The present chiral synthesis was performed with effective stereocontrol of both the chirality in the 1,3-positions on the cyclopropane and the Z-geometry of the propenyl group. (ii) (+)-Grandisol, an insect sex pheromone possessing a characteristic cyclobutane structure, was synthesized from commercially available cyclopropyl methyl ketone (route A) or from commercially available 3-cyanopropylzinc bromide and 1-bromo-1-methylpropene (route B) in 10 or 8 steps in 6 % or 8 % overall yield and with 80 % ee. This sequence involves a Shi asymmetric epoxidation of a trisubstituted olefin and a straightforward Stork-type asymmetric cyclobutane formation with clean SN2 stereoinversion using the nitrile α-anion of the chiral epoxynitrile. The present expedient method is the second asymmetric total synthesis starting from achiral compounds.

(1R,2S,6R)-Papayanal: A new male-specific volatile compound released by the guava weevil Conotrachelus psidii (Coleoptera: Curculionidae)

The guava weevil, Conotrachelus psidii is an aggressive pest of guava (Psidium guajava L.) that causes irreparable damages inside the fruit. The volatile compounds of male and female insects were separately collected by headspace solid-phase microextraction or with dynamic headspace collection on a polymer sorbent, and comparatively analyzed by GC-MS. (1R,2S,6R)-2-Hydroxymethyl-2,6-dimethyl-3-oxabicyclo[4.2.0]octane (papayanol), and (1R,2S,6R)-2,6-dimethyl-3-oxabicyclo[4.2.0]octane-2-carbaldehyde (papayanal) were identified (ratio of 9:1, respectively) as male-specific guava weevil volatiles. Papayanal structure was confirmed by comparison of spectroscopic (EIMS) and chromatographic (retention time) data with those of the synthetic pure compound. The behavioral response of the above-mentioned compounds was studied in a Y-tube olfactometer bioassay, and their role as aggregation pheromone candidate components was suggested in this species.

NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A

The present invention relates to compounds of the formula I and their salts etc. which are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders. wherein Y1 and Y2 are adjacent atoms in Het1, which are independently selected from the group consisting of carbon and nitrogen; k is 0, 1, 2 or 3; Het1 is a bivalent monocyclic 5- or 6-membered heteroaromatic radical, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, N and N—Ra as ring members, or a bivalent fused bicyclic 8-, 9- or 10-membered heteroaromatic radical, having 1, 2, 3 or 4 heteroatoms or heteroatom moieties selected from O, S, N and N—Ra as ring members; Het2 is inter alia monocyclic 5- or 6-membered hetaryl, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, N and N—R1a as ring members, Cyc is inter alia optionally substituted monocyclic 5- or 6-membered hetaryl or optionally substituted fused 8-, 9- or 10-membered bicyclic hetaryl; Ar is optionally substituted phenylene or optionally substituted bivalent 6-membered hetaryl; R is attached to a carbon atom of Het1 and inter alia-halogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy, C1-C6-fluoroalkyl, C1-C6-fluoroalkoxy, C3-C6-cycloalkyl etc.

A highly stereocontrolled formal total synthesis of (±)- and of (-)-grandisol by 1,4-conjugated addition of organocopper reagents to cyclobutylidene derivatives

Starting from suitable cyclopropanes, a formal total synthesis of racemic grandisol and of the enantiopure (-)-grandisol is presented. The racemic synthesis of the grandisol precursor was accomplished in five steps. The synthesis of the chiral non-racemic precursor (1S,2S,2′R)-cis of this pheromone was realized in 10 steps, with an overall yield of 45%, using the enantiopure cyclobutanone (R,S), previously obtained by ring expansion of an optically pure oxaspiropentane. The key stereodefining step was the addition of lithium dimethylcuprate to a chiral α,β-unsaturated cyclobutylidene carbonyl derivative.

Stereospecific palladium(0)-catalyzed reduction of 2-cyclobutylidenepropyl esters. A versatile preparation of diastereomeric monoterpenoids: (±)-fragranol and (±)-grandisol

Mixtures of (E and Z)-2-cyclobutylidenepropyl sulfonates, readily available from α,α-disubstituted cyclobutanones arising from suitable cyclopropane derivatives ring expansion, underwent regioselective and stereospecific reduction by formate anion to offer, through π-1,1- trimethyleneallylpalladium complexes formed upon treatment with palladium(0), a new and convenient entry to the diastereomeric four-membered ring monoterpenoids (±)-fragranol and (±)-grandisol.

Identification of novel inhibitors of the transforming growth factor β1 (TGF-β1) type 1 receptor (ALK5)

Screening of our internal compound collection for inhibitors of the transforming growth factor β1 (TGF-β1) type I receptor (ALK5) identified several hits. Optimization of the dihydropyrroloimidazole hit 2 by introduction of a 2-pyridine and 3,4-methylenedioxyphenyl group gave 7, a selective ALK5 inhibitor. With this information, optimization of the triarylimidazole hit 8 gave the selective inhibitor 14, which inhibits TGF-β1-induced fibronectin mRNA formation while displaying no measurable cytotoxicity in the 48 h XTT assay.