Hydroxymethylene group

Since double bonds may be considered as masked carbonyl, carboxyl or hydroxymethylene groups, depending on whether oxidative or reductive methods are applied after cleavage of the double bond, the addition products from (E)-2 and carbonyl compounds can be further transformed into a variety of chiral compounds. Thus, performing a second bromine/lithium exchange on compound 4, and subsequent protonation, afforded the olefin 5. Ozonolysis followed by reduction with lithium aluminum hydride gave (S)-l-phenyl-l,2-ethanediol in >98% ee. 

In acetic acid the intermediate zwitterion is trapped by acetate affording cyclopentenones with an acylated hydroxymethylene group on C-4. Use of this sequence has been made of in the synthesis of the sesquiterpenes cyclocolorenone 347) (3.31) and a-cadinol (3.32) 348). 

Thus N6-(3-iodobenzyl)adenosine (MRS541, structure not shown) acts as partial agonist (46% A3 efficacy) while the 2-chloro-N6-(3-iodobenzyl)adenosine (MRS542, structure not shown) behaves as potent but non selective A3 AR antagonists (K. A3 = 1.8 nM, EC50 A2B > 10,000 nM, K A2a = 197 nM, K A, = 16.8 nM) (Gao et al. 2006). It has to be remarked that the efficacy of the latter compound is completely restored by the replacement of the 4 -hydroxymethylene group with a 5 -methyluronamide function (Cl-IB-MECA). 

A moderate yield of this reaction may be due to side reactions like dimethyl acetal formation at the hydroxymethylene group. 9 Alkylating reagents like dimethyl sulfate or diazomethane6d have been employed as well to furnish the enol ether moiety in 1 but proved to give lower yields. 

The boronic acid binding site can also be used for interactions with monoalcohols. In the presence of an ort/zo-hydroxymethylene group (see entry 1), an intramolecular cyclic monoester is formed (boronophthalide). This compound still has one hydroxyl group left for the esterification of monoalcohols, a reaction that can be used in the imprinting procedure [46,47,72]. Recently this method has been revived for the binding of steroid alcohols [73,986,c]. 

An interesting chemical characteristic of the hydroxymethylene group at C-2 of various branched penteno-y-lactones [108] can be observed during the oxidation of vicinal diols with periodate which proceeds with extremely high selectivity with the relative rates 100 1 3 100. Thus, the isomers with cis- and trans-2,3-diols can be readily identified. 

Allylation of the pyrido[l,2-a]quinazoline-l,5-dione 136 (R = Ph, Ar = Ph) with allyl bromide afforded the corresponding 3-allyloxy derivatives. The hydroxymethylene group of the azepino[l,2-a]quinazolinone 142 was acetylated with acetyl chloride. When the cyclopenta[e]pyrido[l,2-a]py-rimidine-4-thione 160 (n = 0) was treated with methyl io de, a quaternary salt (177) was obtained. ... 

To create a new chiral center at C(2) and to introduce a hydroxymethylene group simultaneously, Dondoni s method26 was used. Treatment of the aldehyde 96 with 2-(trimethylsilyl)thiazole 89 afforded the highly diastereoselective adduct 97, but it had an undesired configuration at the new chiral center. The high diastereoselectivity is attributed to the preferred transition state D. 

Compound (12) was identified as a triterpene of the friedelin type, with a structure very similar to (11), except for the shift of the position of the hydroxymethylene group in (12). The position of this group and its stereochemistry was determined by means of HMBC and NOESY experiments, locating it on C-17. 

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