Addition reactions biologically active compounds

In addition, demercuriation reactions have resulted in a wide variety of rather complex compounds including aromatic aminoacids, steroids, imidazols, etc. in good yields (at the tracer level). The driving force in these studies has been the hope of incorporating At into biologically active compounds for therapautic use. 

In addition to terpenes (as described above), carbohydrates have also been used as substrates in domino metathesis reactions, the aim being to synthesize enan-tiopure polyhydroxylated carbocyclic rings. These structures are components of several biologically active compounds such as aminoglycoside antibiotics [254], inositol phosphates [255], and carbanucleosides [256]. An efficient entry to this skeleton was developed by Madsen s group using a domino RCM/CM of the carbohy-... 

Addition of Heterocyclic Compounds Stereocontrolled nucleophilic addition of heterocyclic compounds to chiral nitrones is of great synthetic importance in the synthesis of natural and biologically active compounds. In these reactions, the nitrone group serves as an amino group precursor and the heterocycle furnishes the formyl group (from thiazole) (192, 195, 214, 215, 579) or the carboxyl group (fromfuran) (194-196, 580-584) (Scheme 2.149). 

The conjugate addition of organometallic reagents to a./i-unsaturated compounds is one of the basic methods in our repertoire for the construction of carbon-carbon bonds. These addition reactions have been used as key steps in the synthesis of numerous biologically active compounds, and show a broad scope due to the large variety of donor and acceptor compounds that can be employed. It is evident that a tremendous effort has been devoted over the last three decades to develop asymmetric variants of this reaction. ... 

We and others have demonstrated facile synthesis of a number of new anticancer active p-lactams. The p-lactam derivatives described herein are unique, and they demonstrate reasonable in vitro antitumor cytotoxicity. The stereochemical outcome of the Staudinger reaction as reported herein may offer our laboratory and others many additional opportunities to use p-lactams in the synthesis of biologically active compounds. Although the mechanism of action of the lead compounds has not been totally established, our research on cell cycle analysis offers intriguing... 

Both pyrimidines [46] and 3-nitro-2-pyridones [48-53] are often found in biologically active compounds or their synthetic intermediates. The present TCRT will be a useful protocol for construction of a useful library, however, it is required to control the selectivity of these products from the viewpoint of atom economy. The addition of acetic acid is influential for the selectivity of this reaction, and the results are summarized in Table 3. 

This reaction is particularly suitable for the preparation of the Wieland-Miescher ketone 96, a very useful building block for construction of a broad variety of biologically active compounds such as steroids, terpenoids, and taxol. On the basis of the proline-catalyzed approach described above Barbas et al. recently reported an optimized procedure for formation of the chiral Wieland-Miescher ketone, 96 [105]. It has been shown that this synthesis (which comprises three reactions) can be performed as a one-pot synthesis. The desired product is obtained in 49% yield with enantioselectivity of 76% ee (Scheme 6.43). Here L-proline functions as an efficient catalyst for all three reaction steps (Michael-addition, cydiza-tion, dehydration). It is also worth noting that although many other amino adds and derivatives thereof were tested as potential alternative catalysts, L-proline had the best catalytic properties for synthesis of 96. This result emphasizes the superior catalytic properties of proline reported after previous comparative studies by the Hajos group [100, 101]. 

In summary, the potential utility of the metal catalyzed hydroboration reaction is vast. Future work will focus on its applicability in the synthesis of biologically active compounds where conventional electrophihc additions have proven ineffective. Convenience and mild conditions required for these reactions provide the organic chemist with a valuable synthetic tool. 

Chiral sulfoxides will act as directing groups in asymmetric reactions. An example is in the conjugate addition of a Grignard reagent to an enone (14) to yield the chiral 3-methylcyclopentanone (15) (Scheme 9). Chiral sulfoxides may also be applied to the asymmetric synthesis of biologically active compounds.3... 

Cp2TiCl2 reacts with MgCIPr1 in the presence of cycloheptatriene to give 73-cycloheptadienyltitanium isomers (Scheme 491), which undergo in situ addition to aldehydes to produce a mixture of 1,3- and 1,4-cycloheptadienyl alkyl (aryl) carbinols. The reaction opens a simple way to functionalized 1,4-cycloheptadienes, some of which are closely related to biologically active compounds.1159... 

Enantiopure diaryl methanols (1) are important intermediates for the synthesis of biologically active compounds.[1] Here, a synthetic approach which employs aromatic aldehydes and readily accessible and commercially available aryl boronic acids is reported.[2,3] The catalysis with planar chiral ferrocene (2)[4] yields a broad range of optically active diaryl methanols with excellent enantioselectivities. Upon addition of DiMPEG (dimethoxy polyethyleneglycol) to the reaction mixture the enantioselectivity is increased. 

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