7-Hydroxymethyl-2-substituted 7- methyl derivatives

C-6 methyl- and hydroxymethyl-substituted Neu5Ac2en derivatives 154 [97], and the 6-thio-Neu5Ac2en derivative 155 [78] have been synthesised. 

AT-[(Acyloxy)methyl] derivatives of active amines and amides have the general formula RK N-CHR O-COR " where R" = H or Me (or an even larger substituent) and COR" is the acyl group. Activation of these derivatives occurs in two steps as depicted in Fig. 8.20, by analogy with the biotransformation of 0-[(acyloxy)methyl] derivatives of phenols (Sect. 8.5.6) [62], The first step is enzymatic or nonenzymatic cleavage of the ester bridge (Fig. 8.20,a), followed by chemical breakdown of the A-(hydroxymethyl) intermediate (see also Chapt. 5 in [81]). Here, again, liberation of toxic formaldehyde, i. e., where R" = H, should be avoided whenever possible by substitution of, e.g., Me at R"... 

The structure of the phenylcoumarone (XXII) 26) was derived from analytical and spectral investigation and was confirmed by a synthesis 29) starting from dehydrodiconiferyl alcohol (XXVII). The latter compound (XXVII) was converted by monoperphthalic acid into an epoxide whose side chain was equivalent to that of an arylglycerol. By properly performed acidolysis, the epoxide side chain therefore was converted into the primary ketol structure, and at the same time the hydroxymethyl-substituted phenylcoumaran system see XXVII) was converted into the methyl-substituted phenylcoumarone system of XXII (Figure 8). 

The starting substrate, protected ot-vinylproline 187 was activated by HATU and coupled with glycine methyl ester hydrochloride to give protected peptide derivatives 188. Further, ozonolysis of these derivatives and subsequent reduction with excess of Na[BH(OAc)3] provided the hydroxymethyl-substituted derivative 189 in... 

Prenyl-naphthohydroquinone-2-carboxyhc acid is the key intermediate in the formation of anthraquinones of the alizarin type. (In contrast the A-ring-substituted anthraquinone derivatives found in fungi and certain higher plants, e.g., Rhamnaceae and Polygonaceae, are polyketides, D 3.3.5). In the biosynthesis of alizarin one C-atom of the isoprene residue is lost. In structurally related compounds, however, this C-atom may still be present in the form of a methyl, hydroxymethyl, aldehyde, or carboxy group. 

The H- and C-n.m.r. spectra of sucrose, methyl a-D-fructofuranoside (20) and methyl P D-fhictofuranoside (21) with single sites of C-substitution at C-1, C-2, C-3-, or C-6 of the furanose moieties have been analysed to assess the conformations of the their furanose rings, and of the glycosidic linkages in aqueous solution. In addition, spin-couplings in 20 and 21 were compared with those of a-(22) and p-D-r/jrco-pentulofuranose (23), respectively, to study the effect of glycosidation and hydroxymethyl substitution on the solution conformations. The conformations of 2-mono- and 2,2 -di-G-substituted a,a-trehalose derivatives 25 have been shown by n.m.r. spectroscopy in combination with molecular mechanics calculations, to differ from that of the 2,2 -unsubstituted disaccharide 24, both in solution and in the solid state. N.O.e. experiments on the 6 -deoxy-, 6 -thio-, and 6 -0-THP derivatives of methyl 2-acetamido-2-deoxy-P-lactoside, potential inhibitors of (2- 6)-a-sialyltransferase, proved that they adopt the same conformation as the parent compound. ... 

The 8-methyl-8,14-cycloberbine 364, derived from the protoberberine 324 via the betaine 363, was reduced with sodium borohydride or lithium aluminum tri-tert-butoxyhydride to give a diastereoisomeric mixture of cis-and trans-alcohols (7.8 1 or 1 7.8, respectively) (Scheme 64).t)n exposure to formaldehyde the mixture underwent N-hydroxymethylation and subsequent intramolecular substitution on the aziridine ring to give the oxazolidine 365. Removal of the hydroxyl group in 365 was accomplished by chlorination followed by hydrogenolysis with tributyltin hydride. Reductive opening of the oxazolidine 366 with sodium cyanoborohydride afforded ( )-raddeanamine (360), which has already been converted to ochotensimine (282) by dehydration. 

The bromine atom of 4-aryl-2-(4-bromobutyl)-2,3,5,6,7,8-hexahydro-177- ancj -perhydropyrido[l,2-c]pyrimidine-l,3-diones was displaced with 4-substituted piperazines <2002FES959, 2004APH139, 2004PHA99>. Heating 3-hydroxymethyl derivatives of epimeric 6-methyl-l,3,4,6,7,llb-hexahydro-277-pyrimido[6,l-,2]isoquinolin-2-ones 152 resulted in the formation of the 3-unsubstituted derivatives 153 by loss of CH20 (Equation 26) <1997LA1165>. 

Stepanov et a/.143,144 report the ring opening of the monoxide (116) to several 2-oxaadamantane derivatives, where 116 is readily obtained by perbenzoic acid oxidation of 35. Treatment of 116 under various conditions yields different products. Thus, with aqueous acid it yields l-hydroxy-3-hydroxymethyl-2-oxaadamantane (117), with alcohols (R = CH3, C2H5) in acidic or basic media 1-alkoxy-substituted (118), and with hydrochloric acid l-chloro-3-hydroxymethyl-2-oxaadamantane(119). l-Methyl-2-oxaadaman-tane (120) is prepared by LAH reduction of the carbonyl group in 35 to alcohol 121 and subsequent cyclization with acid.140,142... 

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