Phthalimide alkaloids

Asymmetric hydrogenation of Scheme 1.101 provides a general route to isoquinoline alkaloids (see Section 1.3.1.1). An imine substrate is hydrogenated with the chiral titanocene (/ )-34 to give the S product with 98% ee [346a,b,352], A neutral BCPM-Ir complex with phthalimide in toluene also shows high enantioselection [358]. The choice of a weakly polar... 

Heating these products (endo and exo mixtures) was also a source of thiocarbonyl compounds, by cycloreversion [213], and led, in the presence of a diene, to different adducts (exo rich equilibrium mixtures). These reactions were applied in the field of morpholine alkaloids and thioshikimic acid synthesis [5]. Another effective source of thioaldehydes are sulfenyl phthalimides [214], which are very prone to elimination, as described hereunder in the work of Capozzi. 

Coyle and Bryant have reported the efficient synthesis of a triazabicyclo[3.3.0]octane system by the photocyclization of hydantoin derivatives. Thus irradiation of (295), synthesized by standard Mannich procedures, afforded the bicyclooctanes (296) in moderate to good yields. The process, akin to Norrish Type II behaviour, is a 1,6-hydrogen transfer followed by bonding in the resultant biradical (297). The bis-Mannich base compound (298) also photocyclizes, yielding (299). Coyle and his co-workers have also successfully applied the known reactivity of phthalimides to yield polycyclic compounds. Thus irradiation of (300) affords the cyclized compound (301). This can be converted into the protoberberine alkaloid skeleton (302) by treatment with aqueous HCl. The crown ether analogues (303) and (304) have... 

An imine-enamine annulation has been used in the synthesis of the indoloquinolizidine alkaloid ( )-deplancheine.52 The annulation of dialkyl (1-alkoxycarbonyl)vinylphosphonates via a Horner-Wadsworth-Emmons reaction has been developed in the synthesis of [3.3.0] fused pyrazolid-inones from monocyclic pyrazolidinones. - Treannent of diethyl l-(ethoxycarbonyl)vinylphos-phonate in excess (2 eq) with imide anions such as phthalimide, maleimide, and succinimide successfully produces the corresponding six-membered fused heterocycles. Similarly, synthesis of functionalized cyclohexenylphosphonates is achieved by condensation of diethyl l-(ethoxycar-bonyl)vinylphosphonate (2 eq) with cyclopentanone enolates (Scheme 8.29). - ... 

As a graduate student at Manchester, Manske determined the structures of harmine and harmaline and synthesized both alkaloids. He also synthesized rutaecarpine, as he liked to recall, by accident. Another fortuitous experiment was his discovery of the use of hydrazine in the hydrolysis of phthalimides. He also collaborated at this time with A. Lapworth in one of the pioneering studies of physical organic chemistry. He was awarded the Ph.D. by Manchester in 1926. 

Interest in alkaloids of the nicotine group appears to be on the increase. A review has appeared covering tobacco-specific nitrosamines, which may be causative factors in tobacco-related cancers. The solution conformation, and proton, deuterium, carbon-13, and nitrogen-15 n.m.r. spectra of nicotine and its 2- and 4-isomers, have been studied. A new synthesis of nornicotine and nicotine has been described, and a quantitative carbon-13 n.m.r. spectral analysis of nicotine that is labelled at positions 1, 2, and 3 with carbon-13 been presented. The synthesis and mass spectrometry of several structurally related nicotinoids have been reported. Nicotine is dehydrogenated on irradiation in benzene solution in the presence of benzophenone to l -methyl-2 -(3-pyri-dyl)pyrrole. ° Nornicotine has been synthesized in four steps from 3-bromo-pyridine and N-3-butenyl-phthalimide, using a palladium-catalysed vinylic... 

The use of secondary amides as nucleophiles has been also documented by Mori et al.f Synthesis of imides by this method is not always satisfactory, but phthalimides are prepared in high yield (Scheme 44). An interesting modification of this method consists of the double carbonylation of o-aryl diiodides and proceeds via an initial intermole-cular amidation, followed by the intramolecular one described by Mori (Scheme 45). ° The formation of seven-membered rings was demonstrated by the synthesis of diazepam and a number of anthramycin alkaloids, including Prothracarcin and Tomaymycin (Scheme 46). As mentioned above, for seven-membered rings direct amination is observed as a side reaction. Secondary ureas are also substrates for this reaction, yielding seven-membered cyclic ureas. ... 

A subsequent study by Jprgensen et al. also demonstrated the enantioselective a-sulfenylation of (S-dicarbonyl compounds 420 using l-alkylsulfanyl[l,2,4]triazole derivatives 419 in the presence of a catalytic amount of cinchona alkaloid derivative 421. The use of cyclic (S-dicarbonyl compounds ensured the introduction of a quaternary sulfur center however, the observed enantioselectivity was modest in 51-89%. In 2009, Zhu and co-workers reported that a chiral a,a-diaryl prolinol 424 efficiently catalyzed the enantioselective sulfenylation of (S-ketoesters 420 using N-(phenylthio)phthalimide 423 as a sulfur electrophile. The absence of racemizable C—H bonds led to the optically enriched a-sulfenylated products 425 in excellent enantio-selectivities. In 2010, Fu developed a method for catalytic asymmetric 7-sulfenylation of carbonyl compounds using 2,3-allenoates 426 in the presence of a chiral bisphos-phine, TangPhos 427, and a bulky carboxylic acid 428. ... 

Phorbol, T39 Phosphatidic acids, AIS Phosphatidylglycerol, A15 Phosphonomycin, Y20 Phosphorus compounds, A14, AIS, Y20, Y24, XIO, Z3-Z6, Z3-4 Photothebainehydroquinone, K4 Phthalideisoquinoline alkaloids, K3 Phthalides, AS 1 Phthalimides, A9 Phyllantidine, K18 Phyllocladene, T36... 

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