Chiral Carbocyclic Nucleosides Research Articles

The Enantioselective Synthesis of Chiral Carbocyclic Nucleosides via Palladium‐Catalyzed Asymmetric Allylic Amination of Alicyclic MBH Adducts with Purines

AbstractThe enantioselective synthesis of carbocyclic nucleosides through the palladium‐catalyzed asymmetric allylic amination of alicyclic Morita‐Baylis‐Hillman (MBH) adducts with purines was successfully developed. With a combination of Pd2(dba)3/L7 as catalyst, various optically active carbocyclic nucleosides featuring a C=C double bond in the carbocycle moiety were obtained in high yields (up to 97%) with excellent N9/N7‐selectivities (>95/5) and enantioselectivities (up to >99.6%). In addition, these nucleoside analogs allowed for rapid transformation to a variety of other interesting structurally diverse chiral carbocyclic nucleosides.magnified image

Asymmetric Transfer Hydrogenation of rac-α-(Purin-9-yl)cyclopentones via Dynamic Kinetic Resolution for the Construction of Carbocyclic Nucleosides.

An asymmetric transfer hydrogenation via dynamic kinetic resolution of a broad range of rac- α-(purin-9-yl)cyclopentones was first developed. A series of cis-β-(purin-9-yl)cyclopentanols were obtained with up to 97% yield, >20/1 dr, and >99% ee. This also provides an efficient synthetic route to a variety of chiral carbocyclic nucleosides.

Enantioselective Synthesis of Carbocyclic Nucleosides via Asymmetric [3 + 2] Annulation of α-Purine-Substituted Acrylates with MBH Carbonates.

An efficient route to chiral carbocyclic nucleoside analogues containing a quaternary stereocenter and a C═C double bond has been established via a highly enantioselective [3 + 2] annulation of Morita-Baylis-Hillman (MBH) carbonates with α-purine-substituted acrylates. With 20 mol % (S)-SITCP as the catalyst, various chiral carbocyclic nucleoside analogues with a quaternary stereocenter and a C═C double bond were obtained in high yields (up to 92%) with good diastereoselectivities (up to 10:1 dr) and excellent enantioselectivities (up to 96% ee). Furthermore, the corresponding products were subjected to diverse transformations to afford interesting and potentially useful chiral carbocyclic nucleosides.

ChemInform Abstract: Rhodium‐Catalyzed Desymmetrization by Hydroformylation of Cyclopentenes: Synthesis of Chiral Carbocyclic Nucleosides.

AbstractA Rh‐catalyzed desymmetric hydroformylation of 3‐substituted cyclopentenes constitutes an efficient approach to chiral cyclopentane carboxyaldehydes.

Rhodium-Catalyzed Desymmetrization by Hydroformylation of Cyclopentenes: Synthesis of Chiral Carbocyclic Nucleosides.

Excellent enantioselectivities (up to 97 % ee) and diastereoselectivities (up to >99:1 d.r.) have been achieved in the desymmetrization of cyclopentenes by catalytic hydroformylation. This novel methodology provides an efficient and concise synthetic route to chiral cyclopentane carboxaldehydes. The key intermediate, (1S,3S)-(3-hydroxymethyl)cyclopentanol, for the synthesis of carbocyclic-ddA was obtained in three steps.

Rhodium‐Catalyzed Desymmetrization by Hydroformylation of Cyclopentenes: Synthesis of Chiral Carbocyclic Nucleosides

AbstractExcellent enantioselectivities (up to 97 % ee) and diastereoselectivities (up to >99:1 d.r.) have been achieved in the desymmetrization of cyclopentenes by catalytic hydroformylation. This novel methodology provides an efficient and concise synthetic route to chiral cyclopentane carboxaldehydes. The key intermediate, (1S,3S)‐(3‐hydroxymethyl)cyclopentanol, for the synthesis of carbocyclic‐ddA was obtained in three steps.

ChemInform Abstract: A Straightforward Entry to Chiral Carbocyclic Nucleoside Analogues via the Enantioselective [3 + 2] Cycloaddition of α‐Nucleobase Substituted Acrylates.

A straightforward entry to chiral carbocyclic nucleoside analogues has been realized via the enantioselective [3+2] cycloaddition of α-nucleobase substituted acrylates to vinyl cyclopropanes for the first time. With Pd2(dba)3-L5 as the catalyst, carbocyclic purine, uracil, and thymine nucleoside analogues with quaternary stereocenters were obtained in excellent yields (up to 99% yield) and good enantioselectivities (up to 92% ee).

A straightforward entry to chiral carbocyclic nucleoside analogues via the enantioselective [3+2] cycloaddition of α-nucleobase substituted acrylates.

A straightforward entry to chiral carbocyclic nucleoside analogues has been realized via the enantioselective [3+2] cycloaddition of α-nucleobase substituted acrylates to vinyl cyclopropanes for the first time. With Pd2(dba)3-L5 as the catalyst, carbocyclic purine, uracil, and thymine nucleoside analogues with quaternary stereocenters were obtained in excellent yields (up to 99% yield) and good enantioselectivities (up to 92% ee).

Carbocyclic nucleosides from enantiomeric, α-pinane-based aminodiols

Starting from (1 R,2 S,3 S,5 R)- and (1 S,2 R,3 R,5 S)-6,6-dimethylspiro[bicyclo[3.1.1]heptane-2,2’-oxiran]-3-ol (−)- 8 and (+)- 8, two comparative syntheses were developed for pinane-based chiral carbocyclic nucleosides. The regioselective ring opening of the spiro-oxirane ring of (−)- 8 and (+)- 8 with NaN 3 resulted in azidodiols (−)- 9 and (+)- 9. Catalytic reduction of (−)- 9 and (+)- 9 furnished chiral aminodiols (−)- 10 and (+)- 10, which were transformed by linear synthesis to purine-type nucleosides 16– 18 through pyrimidine intermediates. Regioselective ring opening of the oxirane ring of (−)- 8 and (+)- 8 resulted in adenine-, cytosine- and uracil-based carbocyclic nucleosides 19– 21 in a single-step synthesis.

A synthetic approach to chiral carbocyclic nucleosides of varied ring-sizes using carbon framework of D-glucose

Synthesis of enantiomerically pure carbocyclic nucleoside analogues 10-16 with five-, sixand sevenmembered rings has been achieved starting from D-glucose derived tetracyclic isoxazolidinocarbocycle precursors 1-3. Cyclization of 6-chloro pyrimidine derivatives 7-9 to purine derivatives was found to be accomplished by nucleophilic displacement of 6-chloro substituent (by dimethylamino and/or methoxy groups). Apparently, hydrogen bonding between N-3 of the purine ring and a hydoxy substituent at C-2 plays a crucial role in this transformation.

Artificial oligonucleotides consisting of an analog of nucleoside antibiotics, carbocyclic oxetanocins

Modified oligonucleotides, hexadecamers, containing carbocyclic analogues of oxetanocin A and T, have been synthesized from the corresponding chiral carbocyclic nucleosides. The oligonucleotide derived from carbocyclic oxetanocin A forms a stable triple-helix with uridine oligoribonucleotide even under physiological conditions.

Chiral Carbocyclic Nucleosides from d-Glucose: Enantiodivergent Synthesis and One-Pot Entry of Dimethylamino Functionality in the Purine Rings

Cyclization of appropriately designed enose−nitrones derived from d-glucose, having nitrone at C-5 or C-1 and allylic/homoallylic functionalities at C-3 of the sugar backbone, afforded polyhydroxylated aminocarbocycles which were subsequently used as the precursors for carbocyclic nucleoside analogues (11, 13, 16, 21, and 23). The enantiodirecting synthesis of both the enantiomeric pairs of nucleoside analogues 11 and 13, 21a and 23a, and 21c and 23c, has also been demonstrated by judiciously applying intramolecular nitrone cycloaddition (INC) reaction. An interesting observation was that in the cyclization reaction of pyrimidine ring to purine ring in DMF solvent, the substitution of C-6 chloro group with a dimethylamino functionality also occurred spontaneously under mild condition, though similar reactions are reported to occur at higher temperature. The hydrogen bonding between N-3 of the purine ring and an appropriate hydroxy substituent in the carbocycle seems to play a crucial role in this reaction.

A simple route to optically active, functionalized five-, six- and seven-membered carbocyclic derivatives

The isoxazolidinocarbocyclic derivatives 6, 7 and 13, useful as precursors for unnatural bioactive chiral carbocyclic nucleosides and for glycosidase inhibitors have been synthesized from D-glucose through intramolecular 1,3-dipolar cycloaddition.

ChemInform Abstract: Chiral Carbocyclic Nucleosides: The Synthesis and Antiviral Activity of 4′‐Hydroxy‐ and 4′‐Fluorocarbocyclic 2′‐Deoxyguanosines.

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.

Chiral carbocylic nucleosides: The synthesis and antiviral activity of 4′-hydroxy and 4′-fluorocarbocyclic - 2′- deoxyguanosines

The chiral carbocyclic nucleosides 2 and 3 were prepared from aristeromycin. The 4′α-hydroxy compound 2 displays good antiviral activity against HSV-1 and HSV-2 with low toxicity.

ChemInform Abstract: Synthesis of Chiral Carbocyclic Nucleosides

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.

Synthesis of chiral carbocyclic nucleosides

Synthesis of chiral carbocyclic nucleosides