Dihydro analogues

The primary fragmentations of 5-methylsulfonyl-6-phenyl-2-pyridone (41) and its 3,4-dihydro analogue (42) are dominated by the methylsulfonyl substituent and not by the pyridone moiety26. Equation (18) summarizes the most important primary fragmentations and shows that the pyridone ions m/z 186 and 170 yield the pyrrole-type ions m/z 158 and 142 only after the sulfonyl side-chain has been broken off. Since the mass spectrum... 

Acyl-substituted quinolizinium ylide 63 was obtained by treatment of its 1,2-dihydro analogue with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ). Its 1,3-dipolar cycloaddition with an acetylenic ester in excess was regioselective and was accelerated in polar solvents yielding the intermediate adduct 64 and finally the corresponding cyclazine 65, as shown in Scheme 2 <2001JOC1638>. 

The imine 217, formed from acetophenone and the 1-aminoimidazole, has been transformed into the enamine 218 which is then cyclized to 219 in trifluoroacetic acid (TFA) (Equation 40) <1995SC3271 >. The diaminoimidazole 220 reacts with ynone 221 to form 222 (Equation 41) <1998CHE1189>. Bromochalcones and chalcone dibromides can also be used in place of the ynone. Similar reactions have been used to prepare the dihydro analogues of 222 <1999CHE1207>. The reaction between 1-aminoimidazoles and 1,3-diketones has been extended to prepare bis-heterocyclic compounds, for example, 223 as ligands for transition metals (Equation 42) <2005EJI4382>. 

The same Japanese group then synthesized numerous 3(2//)-pyridazinones of type (28) bearing a thiocarbamoylalkyl side-chain at N-2 as well as 4,5-dihydro analogues thereof and observed similar activities in this series... 

Among the dihydro analogues of thiouracil, 2-mercapto-6-methyl-5,6-dihydro-uracil (LXXX) retains some of the antithyroid activity exhibited by 2-thiouracils [642] (see Part 1 of this review. Volume 6). This compound can be obtained either by the condensation of thiourea with ethyl crotonate or by the hydrogenation of 2-mercapto-6-methyluracil. 

Dihydroquinazolines can be aromatized by the same procedures used for the dihydropyrimidines <2000T9343, 2002JFC(118)73, 2006JOC1969, 2006T9726>, and thus the tetrahydroquinazolinedione 549 gave the dihydro analogue 550 in 61% yield with CAN and NaHCOs <2006T9726>. 

Peroxyacids oxidize the imine group in (236) and related compounds to the nitrone. The 1,4-benzodiazepine (178) and its 4,5-dihydro analogue can be oxidized to the 2-oxo derivatives with chromium(VI) oxide. The benzodiazepinone (236) can be hydroxylated at the 3-position via a two-step process firstly reaction with LTA gives the 3-acetoxy derivative and this can then be hydrolyzed in high yield using sodium methoxide in methanol/methylene chloride. The 3-acetoxy derivative may also be prepared via bromina-tion with NBS and reaction with sodium acetate in situ (79JHC1449). 

The 1,2,5-benzothiadiazepine 1,1-dioxide (545) and its 3,4-dihydro analogue have been prepared by the reaction of 2-nitrobenzenesulfonyl chloride with w-aminoacetophenone to give (544) followed by reductive cyclization (79JHC835). 

Much of the PMR work on pyran-4-ones has been concerned with the aromatic nature of the system and several reports of aromatic character are based on the downfield shifts relative to non-aromatic dihydro analogues (68T923). The more acidic the solvent used in the spectral studies, the further downfield the signals are shifted. The protonated form (55) is clearly more aromatic and hence this shift is not unexpected, but whether this is a result of ring current is uncertain. 

The identical vicinal coupling constants for 1,4-benzodioxin and 2,3-dihydro-l,4-dioxin, 3.73 Hz, have been cited as evidence to confirm the absence of aromatic character in the former (67AJC1773), and by the same reasoning (22) should also be non-aromatic (70ZC296). The corollary of this argument, however, is that the dissimilar 3/ values for 1,4-dithiin, 6.97 Hz, and its dihydro analogue, 10.02 Hz, indicate substantial aromatic character in the former. However, it has been pointed out that this simple type of comparison fails to allow... 

In some cases the application of a basic catalyst can be followed by further oxidation of dihydropyrimidene-2-thiones, yielding heteroaromatized heterocycles [60, 61]. For example (Scheme 3.14), it was shown that the reaction of 4-oxo-4-arylbut-2-enoic acids 45 with thiourea 28 in the presence of sodium hydroxide led to 2-mercapto-6-arylpyrimidine-4-carboxylic acids 46 [60], while their dihydro analogues were not isolated. 

Basic catalysis of the reactions of urea with unsaturated ketones, as well as thiourea, can lead to heteroaromatization with the formation of oxidized pyrimidinones instead of their dihydro analogues [77] (Scheme 3.23). 

In addition, the ability of dibenzoylethylene to act as a hydride ion acceptor became apparent in the formation (3-adduct 171, dibenzoylethane 172 and triazolopyrimidines 173 and 174, while their dihydro analogues were not observed as reaction products. Another example, involving pyruvic acid derivatives and 3-amino-1,2,4-triazole, will be shown below. 

According to [231, 232], the reactions of 6-aminouracil 294 with chalcones in air lead to pyrido[2,3-d]pyrimidines 296, while their dihydro analogues can be... 

An important feature of the synthesis of heteroaromatized derivatives of azoloazines via their dihydro analogues is high regioselectivity when R is not the same as R2 (Scheme 3.88) in comparison with reactions of aminoazoles with (3-diketones with the same R and R2 substituents. 

Ivermectin possesses a broad spectrum of antiparasitic activities [51] and is a 22,23-dihydro analogue of the macrocyclic lactone, avermectin B,. Ivermectin is highly effective against microfilariae of O. volvulus at very low doses (50-200/ig/kg) [52] and in comparison with DEC, induces only mild mazzotti reactions and other side-effects. Its effectiveness against D. viteae in M. natalenis [38] and D. immitis [53] is also documented. 

A O-Diacetyldihydropseudosolasodine (12a) gave the epimeric pyrrolidines (13) on treatment with bromine. When N-bromosuccinimide was used as oxidant, the ketone (12b) and the pyrrolidine (14) were also formed.17 The WolfF-Kishner reductions of solasodenone (9b) and of the epimeric 4,5 -dihydro-analogues have been reported.18 Solasodine gave the expected 5a,6-epoxide on treatment with perbenzoic acid.19 The preparation of an intermediate in the synthesis of the solanidine alkaloids has been reviewed.20... 

For another dihydro analogue, we wondered about conceptually tying down the ethyl group of arteether (145) by connection to the C-9 methyl as an intriguing assessment of the rotational freedom of the C-10 substituent on activity. To achieve this, an co-alcohol was connected to C-9 in analogue 153, which was in turn cyclized to novel pentacycle 154 (Eq. 18). 

The mass spectra of triazines (39) and (45a,b) each showed a characteristic loss of N2 whereas the fragmentation of the dihydro analogues (46a-c) depended on their tautomerism <83Mi 717-01). 

These compounds include the SS-228Y type, the SF-2315 type, the azicemicin type and the WP 3688-3 type (Scheme 52). Some new analogues of the SS-228Y-type have been discovered (Tables 5-8). The one with the simplest structure is the 2,3 dihydro analogue of SS-228Y, ochracenomicin A (217) [151]. This minor... 

In this category we include phenolic compounds based on the structure of 2-phenyl-4H-l-benzopyran-4-one (flavones, flavonols and related dihydro analogues), the isomeric 3-phenyl derivatives (isoflavonoids, including isoflavans) and other non-pyronic C6-C3-C6 plant pigments such as chalcones, aurones and anthocyanidins. 

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