Monosaccharides cyclization

Monosaccharides Cyclize to Form Hemiacetals Aldehydes can add hydroxyl compounds to the carbonyl group. If a molecule of water is added, the product is an aldehyde hydrate, as shown in figure 12.4. If a molecule of alcohol is added, the product is a hemiacetal the addition of a second alcohol results in an acetal. Sugars readily form intramolecular hemiacetals in cases in which the resulting compound has a five- or six-member ring. 

When an open-chain monosaccharide cyclizes to a pyranose form, a new chirality center is generated at the former carbonyl carbon and two diastereo-mers, called anomers, are prodnced. The hemiacetal carbon atom is referred... 

The hetero-Diels-Alder cyclization reaction of tra s-l-methoxy-3-trimethylsilyloxy-1,3-butadiene (Si) (= Danishefsky s diene) with benzaldehyde (S ) (Scheme 12.23) [217-221] is a promising reaction for evaluating the catalytic properties of Lewis acidic lanthanide centers, and has enormous potential for asymmetric synthesis of natural products (e.g., monosaccharides) [222-225]. 

Monosaccharides not only exist as open chain molecules (acyclic), but also as cyclic compounds. Cyclization leading to the formation of a cyclic... 

Monosaccharides commonly form internal hemiacetals or hemiketals, in which the aldehyde or ketone group joins with a hydroxyl group of the same molecule, creating a cyclic structure this can be represented as a Haworth perspective formula. The carbon atom originally found in the aldehyde or ketone group (the anomeric carbon) can assume either of two configurations, a and /3, which are interconvertible by mutarotation. In the linear form, which is in equilibrium with the cyclized forms, the anomeric carbon is easily oxidized. 

The reversal of the well-known transformation of sugars into pyrans has been detailed as a method for assembling simple monosaccharides from simple furans (71T1973). A compound of the 2-furylcarbinol type was converted by the Br2/MeOH procedure into a mixture of the cis and trans isomers of the corresponding 2,5-dimethoxy-2,5-dihydrofuran derivative (129). Mild acid hydrolysis of (129) resulted in cleavage of the acetal bonds with formation of the dicarbonyl compound (130) which underwent immediate cyclization to 2,3-dideoxy-DL-alk-2-enopyranos-4-ulose (131 Scheme 29). 

Hydrazones 10 derived from aldose monosaccharides (9) and 2-hydrazinopyrimidine (8) gave, upon oxidative cyclization with bromine in methanol, the corresponding 3-(alditol-l-yl)-l,2,4-triazolo[4,3-a]pyrim-idines 11 [97JHC(34)1115] (Scheme 7). 

When a monosaccharide forms a cyclic hemiacetal (or hemiketal), the carbonyl carbon becomes a stereocenter. Thus, cyclization leads to formation of two possible stereoisomers. These isomers are called anomers, and the former carbonyl carbon is called the anomeric carbon. The isomer with the anomeric OH (shown in blue) pointed down is the alpha anomer. The isomer with the anomeric OH (shown in blue) pointed up is the beta anomer. (Figure 12.14)... 

In addition to their work on tricyclic systems, Chmielewski and co-workers have used monosaccharides to obtain polycyclic derivatives of oxacepham. For instance, cyclization of 479 (R2 = Tos or TIBS) in a two-phase system including a phase-transfer catalyst and potassium carbonate gave 480 in 65-90% yields. The protecting group R1 was lost if it was a silyl group, for example, TMS, TBDMS <1998T14065>. 

Resin-based chemistry has been used to construct 480 from 481 by use of boron trifluoride to mediate both the cyclization and cleavage steps <1999AGE1121 >. When the monosaccharide was bound to the polystyrene resin (Merrifield and MPP type) by an alkylsulfonyl linker 482 and cyclization was mediated by 2- r/-butylimino-2-diethylamino-l,3-dimethylperhydro-l,3,2-diazaphosphorine, the reaction had low stereoselectivity and the products included tricyclic oxetanes and oxiranes <2004EJ04177>. The Mitsunobu reaction was used to obtain intramolecular N-alkylation of 483 and formation of 484 <2005AGE3732>. 

Preparation of highly functionalized medium-sized carbocycles (210) and (212), derived from carbohydrates, can also be carried out with the same procedure via 8-endo-trig and 1-exo-trig manners, as shown below (eqs. 3.81, 3.82). Moreover, preparation of (3-C-disaccharide (214) proceeds selectively via 8-endo-trig radical cyclization of two temporarily tethered monosaccharide (213), by means of the addition of a carbohydrate-... 

Polyhydroxylated cyclohexene derivatives such as conduritol A-F (7-12) are important secondary messengers eliciting a wide range of biological responses and have also been widely used as starting materials for advanced organic synthesis (4). RCM opens a particularly concise entry into this class of compounds, not least because of the ready availability of the required cyclization precursors from abundant monosaccharides (5,6). 

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