Nemorensic Acid Research Articles

ChemInform Abstract: The Synthesis of (+)-Nemorensic Acid.

The synthesis of (+)-nemorensic acid in nine steps is described; key steps in the route were the stereoselective Birch reduction of a substituted furan, and addition of allyltrimethylsilane to an oxonium ion at C-5; an X-ray crystal structure of (−)-nemorensic acid provided proof of the relative stereochemistry of the target.

Synthesis of clastro-Lactacystin β-Lactone

The highlight in this total synthesis of clastro-lactacystin β-lactone is the anti-selective reductive aldol reaction of electron-deficient pyrrole A under ammonia-free Birch reduction conditions to construct key intermediate C. The Donohoe group has applied this methodology to the synthesis of other natural products including Nemorensic acid (T. J. Donohoe, J.-B. Guillermin, D. S. Walter J. Chem. Soc., Perkin Trans. 1 2002, 1369-1375) and Secosyrin 1 (T. J. Donohoe, H. O. Sintim Org. Lett. 2004, 6, 2003-2006).

Stereocontrolled Syntheses of the Nemorensic Acids Using 6-Diazoheptane-2,5-dione in Carbonyl Ylide Cycloadditions

Levulinic acid-derived 6-diazoheptane-2,5-dione (9) serves as a common precursor in a formal synthesis of frontalin 19, and in syntheses of cis-nemorensic acid 1, 4-hydroxy-cis-nemorensic acid 2, 3-hydroxy-cis-nemorensic acid 3, and nemorensic acid 4. The key step in these syntheses is the Rh(2)(OAc)(4)-catalyzed tandem carbonyl ylide formation-intermolecular 1,3-dipolar cycloadditions of diazodione 9 with formaldehyde, alkynes or allene, which occur with high regioselectivity. Subsequent oxidative cleavage of the ring originally derived from the cyclic carbonyl ylide intermediate provides a straightforward access to polysubstituted tetrahydrofurans, and in particular an efficient entry to the nemorensic acids. Enantioselective cycloadditions with diazodione 9, using chiral rhodium catalysts, gave cycloadducts in up to 51% ee.

Use of Allene in 1,3‐Dipolar Addition to a Carbonyl Ylide: Syntheses of 3‐Hydroxy‐cis‐nemorensic Acid and Nemorensic Acid.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Use of allene in 1,3-dipolar addition to a carbonyl ylide: syntheses of 3-hydroxy-cis-nemorensic acid and nemorensic acid.

1,3-Dipolar addition of allene to the carbonyl ylide derived from 6-diazoheptane-2,5-dione is the key step in syntheses of 3-hydroxy-cis-nemorensic acid and nemorensic acid.

Oxidative Cyclization Based on Reversing the Polarity of Enol Ethers and Ketene Dithioacetals. Construction of a Tetrahydrofuran Ring and Application to the Synthesis of (+)‐Nemorensic Acid.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Preparation of (+)‐Nemorensic Acid and Approaches to Nemorensine Using the Partial Reduction of Electron Deficient Furans.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Oxidative cyclization based on reversing the polarity of enol ethers and ketene dithioacetals. Construction of a tetrahydrofuran ring and application to the synthesis of (+)-nemorensic Acid.

The utility of oxidative cyclization reactions for the construction of tetrahydrofuran rings has been examined. In these experiments, alcohol nucleophiles were found to be effective traps for radical cation intermediates generated from both enol ether and ketene dithioacetal groups. The reactivity of the alcohol trapping group appeared to lie between that of an enol ether and an allylsilane trapping group. The stereochemical outcome of cyclization reactions originating from the oxidation of an enol ether was found to be controlled by stereoelectronic factors. The utility of these cyclization reactions was illustrated with the synthesis of a key tetrahydrofuran building block for the synthesis of linalool oxide and rotundisine. Cyclization reactions triggered by the oxidation of a ketene dithioacetal led to far greater levels of stereoselectivity. The stereochemical outcome of these reactions was shown to arise from steric factors involving the larger ketene acetal group. The synthetic utility of cyclizations utilizing ketene dithioacetal derived radical cations was demonstrated by completing an asymmetric synthesis of (+)-nemorensic acid. Finally, the reactions were shown to be compatible with the use of an amide nucleophile and the direct formation of a lactone product.

ChemInform Abstract: A Practical Route to Enantiopure, Highly Functionalized Seven‐Membered Carbocycles and Tetrahydrofurans: Concise Synthesis of (+)‐Nemorensic Acid.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Preparation of (+)-nemorensic acid and approaches to nemorensine using the partial reduction of electron deficient furans

Starting from a commercially available furoic acid, the synthesis of (+)-nemorensic acid is described in nine steps, and in 32% overall yield. Key steps in our sequence are a chiral auxiliary controlled, stereoselective, Birch reduction of 3-methyl-2-furoic acid and the stereoselective reaction of an oxonium ion generated within a tetrahydrofuran ring. Attempts to complete the synthesis of nemorensine did not succeed because of the low nucleophilicity of platynecine, the alkaloid base portion of the natural product.

A Practical Route to Enantiopure, Highly Functionalized Seven-Membered Carbocycles and Tetrahydrofurans: Concise Synthesis of (+)-Nemorensic Acid

A Practical Route to Enantiopure, Highly Functionalized Seven-Membered Carbocycles and Tetrahydrofurans: Concise Synthesis of (+)-Nemorensic Acid

A practical route to enantiopure, highly functionalized seven-membered carbocycles and tetrahydrofurans: concise synthesis of (+)-nemorensic Acid.

Highly diastereoselective thermal [5C+2C] intramolecular pyrone-alkene cycloadditions can be achieved by introducing a homochiral p-tolylsulfinyl group at a suitable position of the alkene. The resulting adducts can be readily desulfinylated to give optically active 8-oxabicyclo[3.2.1]octane derivatives. Interestingly, switching from a sulfinyl to a sulfonimidoyl group allows one to reverse the direction of the diastereofacial selectivity and thereby produces oxa-bridged carbocyclic systems enantiomeric to those obtained from the sulfinyl precursors. Cleavage of the oxa-bridge on the desulfurated adducts yields highly functionalized seven-membered carbocyclic derivatives in enantiopure form. Alternative cleavage of the seven-membered carbocycle provides enantiomerically enriched tetrahydrofurans. We have exploited this reaction pathway for the synthesis of the naturally occurring enantiomer of nemorensic acid.

ChemInform Abstract: Anodic Oxidation Reactions: The Total Synthesis of (+)‐Nemorensic Acid.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Anodic oxidation reactions: the total synthesis of (+)-nemorensic acid

The anodic coupling of an enol ether to an oxygen nucleophile has been used as a key step in the total synthesis of (+)-nemorensic acid. The anodic cyclization reaction allows for a reversal in the way the tetrahydrofuran ring of the natural product is normally assembled and thus enables construction of the ring in a highly stereoselective fashion.

The synthesis of (+)-nemorensic acid

The synthesis of (+)-nemorensic acid in nine steps is described; key steps in the route were the stereoselective Birch reduction of a substituted furan, and addition of allyltrimethylsilane to an oxonium ion at C-5; an X-ray crystal structure of (−)-nemorensic acid provided proof of the relative stereochemistry of the target.

Enantiospecific Synthesis of (+)-Nemorensic Acid, a Necic Acid Component of the Macropyrrolizidine Alkaloid, Nemorensine.

A concise enantiospecific synthesis of nemorensic acid 3, a necic acid component of the macropyrrolizidine alkaloid nemorensine 2, isolated from Senecio nemorensis L., is described. Reaction of an epsilon-halo-alpha,beta-unsaturated ester (8), readily accessible from a monoterpene (-)-carvone, with samarium iodide gave a fragmentation product (9), where a carbon-carbon bond cleavage reaction occurred between the gamma and delta positions of the carbonyl group, regioselectively. Deprotection of the silyl group of 9 brought about an intramolecular cyclization to provide tetrahydrofuran derivatives (10), which, upon chemical modification of the side chain, gave nemorensic acid.

5 + 2] Pyrone−Alkene Cycloaddition Approach to Tetrahydrofurans. Expeditious Synthesis of (±)-Nemorensic Acid

5 + 2] Pyrone−Alkene Cycloaddition Approach to Tetrahydrofurans. Expeditious Synthesis of (±)-Nemorensic Acid

Asymmetric synthesis of (+)-nemorensic acid? revision of the stereochemistry of the pyrrolizidine alkaloid nemorensine

(+)-Nemorensic acid, the necic acid constituent of the pyrrolizidine alkaloid nemorensine, is shown to be (2R, 3R,5S)-2-carboxy-2,3,5-trimethyltetrahydrofuranacetic acid by synthesis from (R)-(+)-β-citronellol, and a corrected structure for the parent alkaloid nemorensine is established by a single crystal X-ray analysis.