Carbasugars, Substituted Cyclopentanes, C-ribosides

D-3501 - (1R,2S,3R,4R)-2,3-Dihydroxy-4-(hydroxymethyl)-1-aminocyclopentane


Carbasugars are carbohydrate analogues in which the endocyclic oxygen atom is replaced with a methylene group. This modification increases the molecule stability towards chemical and enzymatic hydrolysis, while mimicking the biological activity of the parent carbohydrate. Carbasugars are generally obtained by chemical synthesis, even though some remarkable examples of them have been isolated from natural sources. Caryose 2 and Calditol 3 are two naturally occurring carba-furanoses isolated from Pseudomonas caryophylli (a plant pathogenic bacteria) and Sulfolobus acidocaldarius, respectively.  Carba-galactopyranose 4 is also a  well known carba-pyranose isolated from natural sources (Streptomyces sp.).(1)

natural carbasugars

Fig 1. Carbasugar containing natural products.

Ribose carbo- analogues and their applications in Medicinal Chemistry.

Naturally occurring carbocyclic analogues of ribose like Aristeromycin 5 (isolated from Streptomyces citricolor) and its unsaturated homologue Neplanocin 6 (from Ampukwiella regularis) have been
extensively studied due to their useful biological properties (mainly antiviral, antibacterial and antifungal).(2)

carba nucleic acids

Fig  2.
Carbocyclic  nucleosides.

The discovery of these two natural products stimulated research (mostly S.A.R studies) and also inspired the development of at least two well known inhibitors of  viral replication approved by the FDA now available on the market, namely Abacavir 7 (anti HIV) and Entecavir 8 (anti Hepatitis).

carbocyclic drugs

Fig 3. Carbocyclic drugs approved by FDA.

Synthetic ribose carbo-analogues, have recently re-gained attention as building blocks in medicinal chemistry for a number of novel applications. For example, in two recent patents C-ribose was incorporated in general formulas 9 and 10 for the development of inhibitors of SUMO and E1 activating enzymes, respectively (3a, b). The inhibition of these enzymes may be effective for the treatment of proliferative, cardiovascular and inflammatory diseases.

patented c-glucosides

Fig 4. General structures of recently patented C-ribose analogues.

In another recent patent carbo-ribose analogues have been also reported as novel CD73 inhibitors to be used as anticancer agents. (4)

Substituted pyridines and pyrimidines 11 and 12  have been recently reported in a publication as IRAK4 kinase inhibitors with improved kinase selectivity, which are promising lead candidates for the development of inflammation mediators.(5)

kinase inhibitors

Fig 5.  Recently reported Kinase inhibitors with high potency and improved selectivity.

Synthesis highlights: Vince Lactam.

Among the various synthetic strategies available for the preparation of carba-glucosides, the use of Vince Lactam 14 proved to be a particularly versatile and scalable approach.(6,7) It is worth
mentioning the fact that a Hetero Diels-Alder reaction of Ciclopentadiene 13 with chlorosulfonyl isocyanate  at room temperature provides  Vince Lactam (γ-lactam) as the major compound. When
the reaction is performed under kinetic conditions (-78° C) the unwanted β-lactam is instead the major compound obtained.

Traditionally chlorosulfonyl isocyanate and tosylisocianate were the reagents used for this transformation, even though the process of making available Vince lactam has been improved over the years.

synthesis Vince Lactam

Fig 7.
Preparation of Vinc e Lactam.

Industrially, Chlorosulfonyl Isocyanate has been successfully replaced with Methanesulfonyl Cyanide providing an economic, high yielding and safe process for the Vince Lactam preparation. Enentiomerically pure lactams 14a and 14b can be obtained efficiently by chemical or enzymatic resolution, for example using by bio-catalytic methods (lactamases), which proved to work well also on production scale.

uses of Vince Lactam

Fig  8. Valuable building blocks from Vince Lactam.

The versatility of the Vince Lactam for the synthesis of carbo-cyclic compounds is shown in scheme above. The double bond functionality for example can be subjected to cyclopropanations, epoxidations, aziridinations and fluorinations, which can also be carried out in a stereo-selective

We are able to provide carba-ribose analogue 1 without scale limitations, get your quotation here!
D-3501 - (1R,2S,3R,4R)-2,3-Dihydroxy-4-(hydroxymethyl)-1-aminocyclopentane

Get a quotation for other Biosynth’s selected cyclopentanes here:

J-500343 - (1R,3S)-3-aminocyclopentanemethanol.
J-500278 - (1R,2R)-2-(acetyloxy)cyclopentane-carbonitrile.
J-500288 - (1R,2R)-Boc-2-amino-1-cyclopentane carboxylic acid.
J-500339 - (1R,3S)-1,3-cyclopentanediol 1-acetate
J-501019 –(Peramivir)-(2S)-3-((S)-1-acetamido-2-ethylbutyl)-4-guanidino-2-hydroxycyclopentanecarboxylic acid
J-520055 - Cis-(+)-1,3-Cyclopentanediol diacetate.
J-800361- 1,3-Cyclopentanediol, mixture of cis and trans.
J-502049 - (E)-methyl 7-((1R,2S,3R,5S)-5-acetoxy-2-(hydroxymethyl)-3-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentyl)hept-5-enoate.

Get a quotation for Vince Lactam here:
J-500358 - (1R,4S)-2-acetyl-2-azabicyclo[2.2.1]Heptan-5-en-3-one


1) International Journal of Carbohydrate Chemistry, Volume 2016, Article ID 4760548 /10.1155/2016/4760548.
2) Medicinal Research Reviews. 6, (1), 1–40. doi:10.1002/med.2610060102.
3) a) WO2015002994A2 b) WO2008019124A1.
4) WO2015164573A1.
5) Bioorg. Med. Chem. Lett. 2015, 3203-3207.
6) Chem. Soc. Rev., 2013, 42, 5056.
7) Chem. Rev. 2012, 112, 4642−4686.


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