Synthesis of Glycosylated Natural Products

2 Synthesis of Glycosylated Natural Products.—The 2-araino-2-deoxy-a-D-glucosyl-m3 o-inositol phosphate (38), which was predicted to have insulin-like activity, has been synthesised, as have 3-0-(2-amino-2-deoxy-a-D-galactopyranosyl)-D-c/iiro-inositol and 6-C)-(a-D-mannopyranosyl)-D-myo-inositol which is a fragment of mycobacteria phospholipids. Compound (39), which is a key substance for the synthesis of distomycin 

was made by use of the corresponding a-mannopyranosyl chloride and the corresponding triol which is solubilized in the THF used by complexing with silver triflate. The -selectivity of the reaction is notable.  

Full details have been published on the synthesis of the (S)- and (R)-3-(7-acyl-l- -sialosyl-glycerols (40), and new preparations of (41) and (42) have been described involving the use of the trichloroacetimidate method of glycosylation. Some of the 

A review of the synthesis of anthracyclinones by elaboration of anthraquinones includes a section on the use of sugars as chiral templates. Glycosylations of the daunomycinones (46)-(48) led to the corresponding daunomycin derivatives (49)-(51). The L-fyxo-, L-arabino- and L-nfeo-isomers of the isorhodomycin compounds (52) have been made and tested for cytotoxicity. Several analogues of the anthracycline antibiotics, eg. (53), having a 1,2,3-triazolyl moiety in the sugar, have been described.  

The 3-p-glucuronide of 18(3-glycyrrhetic acid has been prepared as an immunogen for enzyme immunoassay, and the selective synthesis of the 3-0-/3-D-glucopyranoside of 20(5)-protopanoxadiol (ginsenoside) from selectivity protected 12-0-acetyldamnar-24-en-3p,12 3,20(5)-triol has been described.  

2 Synthesis of Glycosylated Natural Products.- Several of the compounds mentioned above have biological chemical significance this section notes the synthesis of natural glycosides (or related 

In the area of simple terpene glycoside farnesyl fi-D-galactopyranoside and a- and -D-mannopyranoside have been reported as have eighteen monoterpene j8-D-glucopyranosides for an investigation of /S-glucosidase specificity. The soluble silver trifluoroacetate gave appreciably enhanced yields.  

A review has been published on flavone and flavonol glycosides. Specific reports have appeared on the preparation of several sets of o- and jS-4-trifluoromethylunbelliferone glycosides, and on the j8-D-glucopyranosides of several isof lavones.  

Allyl esters have been used for carboxyl group protection in Q-glycopeptide synthesis. Standard glycosylation procedures were used to substitute the hydroxyl groups of serine and threonine H-Cbz esters, and the peptide chains were extended following dealkylation using Pd(0)-catalysed allyl transfers.  

Specifically, glycosylated threonine derivatives have been extended by solid phase peptide methodology to glycosylated hexapeptides related to oncofetal fibronectin the sugars involved were jS-D-GlcNAc and the (1-3)-linked y9-D-Gal derivative of it.  

2 Synthesis of Glycosylated Natural Products.-Sarmentosin 18 which is a potent glutamic-pyruvic transaminase inhibitor has been made from an acetylated glycosyl glycerol derivative.  

Several further exanqiles have been reported of glycosylated amino acids which were then elaborated to glycosylated peptides. These include a glucosylated serine which was converted into a glucosyl cyclic pqitide, glycosylated pqitides, some of which have blood clotting characteristics - these 

In the area of glycosyl ceramides, the plasmalopsychosines 20 and 21 have been synthesized for purposes of study of their biological activity the analogue 22 was also produced. In related work. 

Reagents i, BuaSnO ii. BzCl. iii, MeO- CHjOCCClj iv, K2CO3, MeOH  

The newly discovered iridoid glycoside 36 has been made as its hexa-acetate by condensation of the i r( riate 6-triiyl ether with the required 1,2-cyanoethylidene acetal. Condensation of trimethylsilyl 2,3,4,6-tetra-0-acetyl-/3-D-glucopyranoside with the corresponding alcohol in the presence of boron trifluoride resulted in the production in 80% yield of the acetylated glycoside of the podophyllum lignan 37 with an a,/3-ratio of 5 95P  

Haemophilus influenzae type B, has been reported. The essential carbohydrate component has (3-D-ribofuranosyl units linked to C-1 of ribitol.  

Fmther reference to this work is included in Chapter 14. The unsaturated ring of fully acetalated lactal has been opened to give access to the modified galactocerebroside 33. In the area of glycosylated inositols Vasella has reported compound 34 in connection with studies of activation of hydrojqrl groups for substitution. Compound 35 has been 

In the area of glycoslated steroids the a-L-rhamnosyl derivative of cholesterol has been made by a modified Lewis acid-catalysed route, and several standard syntheses of 17-glucosylated androstane and estradiol derivatives have been reported. Likewise, 3-p-hydroxy-5a-pregnan-20-one has been /3-glucosylated.  

In other areas of medicinal chemistry the synthesis of the anthracycline oxaunomycin and analogues have been completed by glycosylations, and glucosylation of 11-deoxyprostaglandin E has been reported. The anti-tumour etoposide and the triterpene glycyrrhetic acid are other compounds to have been subject to glucosylation and glucuronosylation, respectively. 

In the area of nitrogen-containing natural products the following have been glycosylated the antitumor alkaloid 20(S)-camptothecin, the ergot alkaloids elymoclavine, chancoclavine, lysergol (en mic reaction), and castanospermine.  

The cerebroside (43d) was elaborated following synthesis of the aglycone from 1,2-anhydro-3-0-benzyl-L-glycerol, and in related work the sphingenine derivative (44) and the ovi-position deterring pheromone (45) of a fruit fly have been prepared. 

Deoxybulgecin A (46) has been synthesized as have the glycosyl enkephalin derivatives (47) and glycosylamine analgues.  

Separate glucosylation and galactosylation of hydroxyproline using peracetates and boron trifluoride etherate as catalyst and solid-phase procedures led to compounds (53) and (54), and a further solid-phase process involved treating resin-bonded peptides with the 

A review, dealing mostfy with structure and conformation, has appeared on the flavonoid glycosides of the anthofyanins.  

Of note is a new glycosidation method applicable to the preparation of lignan glycosides for which standard methods are not suitable. The P,P-diphenyl-(A - 

In connection with the finding that perilloside A 17 inhibits rat lens aldose reductase, an extensive range of monoterpene glucosides and their tetraacetates have been synthesized by standard Koenigs-Knorr methods, and the same approach has been used to prepare the 3- and 25-monoglucuronides of 25- 

Glycosylation was effected during the preparation of the deoxytetrahydrodes-mycosin 1, a macrocyclic antibiotic containing mycinose and desosamine.  

---

L. J. Williams, R. M. Garbaccio, and S. J. Danishefsky, Iterative assembly of glycals and glycal derivatives The synthesis of glycosylated natural products and complex oligosaccharides, in B. Ernst, G. W. Hart, and P. Sinay, (Eds.), Carbohydrates in Chemistry and Biology, Vol. 1, Wiley-VCH, Weinheim, 2000, pp. 61-92. 

Synthesis of Glycosylated Natural Products and Their Analogues - Very appreciable interest remains in glycosides having functionalized acyclic aglycons. Dimeric coupling of derivatives of compound 19 led to 20, the core portion of cycloviracin Bi, which is a recently discovered anti-herpes compound. 

Synthesis of Glycosylated Natural Products and Their Analogues. - In the... 

Because of this integration, control of carbohydrate reactivity is increasingly required, not only in the traditional areas of monosaccharide and oligosaccharide synthesis, but also for the preparation of carbohydrate mimics such as C-glycosides and imino sugars, and in the synthesis of glycosylated natural products and intermediates for non-carbohydrate compounds. 

The utility of glycosyl phosphates in the synthesis of C-glycosides was demonstrated in the synthesis of the natural product 8,10-di-O-methyIbergenin 39. Utilizing the O-to-C rearrangement, the key C-aryl linkage was installed and further elaboration afforded the product in good yield. 

---