One-pot Diels–Alder cycloaddition/gold(I)-catalyzed 6-endo-dig cyclization for the synthesis of the complex bicyclo[3.3.1]alkenone framework

• Boubacar Sow,
• Gabriel Bellavance,
• Francis Barabé and
• Louis Barriault

Beilstein J. Org. Chem. 2011, 7, 1007–1013, doi:10.3762/bjoc.7.114

• many important bioactive natural products, and in particular, polycyclic polyprenylated acetylphloroglucinols (PPAPs) (Figure 1) [1]. In the past decades, more than 100 PPAPs exhibiting a wide variety of biological activities (antibiotic, anti-HIV, anti-oxidant, etc.) have been isolated from

Nano copper oxide catalyzed synthesis of symmetrical diaryl sulfides under ligand free conditions

• K. Harsha Vardhan Reddy,
• V. Prakash Reddy,
• A. Ashwan Kumar,
• G. Kranthi and
• Y.V.D. Nageswar

Beilstein J. Org. Chem. 2011, 7, 886–891, doi:10.3762/bjoc.7.101

• reported over the years to establish C–N, C–O, and C–S linkages. Carbon–sulfur bonds are widespread, occurring in numerous pharmaceutically and biologically active compounds [4][5][6][7][8]. A large variety of aryl sulfides are in use for diverse clinical applications in the treatment of cancer [9], HIV

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• a variety of therapeutic areas, e.g., treatment of cancer [16][17][18][19][20], glycosphingolipid storage disorders [21][22], Gaucher’s disease [23], type-II diabetes [24][25][26], other metabolic disorders [10], and viral diseases [27][28] such as HIV [29][30] and hepatitis B [31][32] and C [27][33

• deoxygalactonojirimycin (DGJ). Five-membered iminocyclitols possessing N-alkyl and C1-alkyl substituents form a class of potent antiviral compounds active, e.g., against hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) [49][50][51][52]. Biological activity of this family of

• adopted [8]. 1-Deoxynojirimycin (62; DNJ), the more stable 1-deoxy analogue of nojirimycin, represents the main motif of a large family of iminocyclitols (e.g., 63–66). Although numerous other piperidine iminocyclitols have shown encouraging results against HIV and in cancer therapy, the deoxynojirimycin

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• to azoles in chronic recurrent oropharyngeal candidiasis, allogeneic hematopoietic stem-cell transplantation, and chronic granulomatous disease. Other secondary resistance has been observed in HIV infected patients with chronic recurrent oropharyngeal candidiasis [65][66][67]. Other applications of

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• condensation with the attached hydrazide to furnish the desired triazolopiperazine ring 280 directly. A novel and very promising HIV treatment is Pfizer’s maraviroc (286, Celsentri). HIV uses a member of the G-protein coupled receptor family called CCR-5 as an anchor to attach itself to white blood cells such

• as T-cells and macrophages followed by viral fusion and entry into white blood cells. Maraviroc blocks this pathway by acting as an antagonist for the CCR-5 receptor hence disrupting HIV life cycle. The structural features of this molecule are a geminal difluorocyclohexyl carboxamide which is linked

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• ; tuberculosis; Introduction The incidence of TB is now at an all-time historical high with over 2 billion people infected globally [1]. TB is the leading infectious killer of people with HIV/AIDS and is second only to HIV/AIDS as an infectious cause of death for adults [2]. It is sobering that it has been more

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• = SCH3), respectively. These compounds were further treated with nitrous acid and coupled with different secondary amines to yield the triazenopyrazoles 78. Compounds 78 were tested for biological activity against HIV-1 and herpes simplex viruses, and showed moderate activity against HIV-1 virus (Scheme

A new and facile synthetic approach to substituted 2-thioxoquinazolin-4-ones by the annulation of a pyrimidine derivative

• Nimalini D. Moirangthem and
• Warjeet S. Laitonjam

Beilstein J. Org. Chem. 2010, 6, 1056–1060, doi:10.3762/bjoc.6.120

• are of much interest due to their biological activities [1][2]. Additionally, quinazolines are interesting targets for new method development due to their importance in numerous therapeutic areas. Recently, antitumor [3] and anti-HIV activities [4][5] of quinazolines have been described. A large

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• relationship studies of Indinavir (17, Figure 2), an HIV protease inhibitor developed by Merck. It is a functionalised pseudopeptide containing a central hydroxyethylene moiety in place of a scissile peptide bond. X-ray crystallography shows that 17 binds to HIV protease with its central carbon chain in an

• group. Fluorine atoms have a strong influence on both the electronic and the conformational properties of the sugar moiety, and these effects are illustrated in a series of antiviral compounds 22–25 (Figure 4) [23]. Dideoxy adenosine (22) is an inhibitor of HIV reverse transcriptase, but its clinical

• . Interestingly however, fluorinated isomer 23 is inactive against HIV reverse transcriptase, whereas the diastereomeric compound 24 maintains the potency of the parent compound 22. This result can be explained by the effect of the fluorine atoms on the molecular conformations of 23 and 24 [24]. In isomer 23, the

Symmetrical and unsymmetrical α,ω-nucleobase amide-conjugated systems

• Sławomir Boncel,
• Maciej Mączka,
• Krzysztof K. K. Koziol,
• Radosław Motyka and
• Krzysztof Z. Walczak

Beilstein J. Org. Chem. 2010, 6, No. 34, doi:10.3762/bjoc.6.34

• ]. Furthermore, amide-conjugated systems of solely biologically active units may be utilised in combined anti-HIV therapy, e.g. 2′,3′-dideoxycytidine and 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine conjugate (ddC-HEPT) (VI) [5]. In addition, Shimizu et al. in 2001 reported structures, which are formally α

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• carbohydrates. Such oligosaccharide mimetics are potential therapeutic agents against HIV and other infections, against cancer, diabetes and other metabolic diseases. An efficient strategy to access this type of compounds is the replacement of the glycosidic linkage by amide or pseudoamide functions such as

• and exhibit interesting biological activities. Thus, the O-sulfated β(1→2) and β(1→6)-linked homo-oligomers effectively inhibit L-selectin-mediated cell adhesion, HIV infection and heparanase acitivity in a linkage-specific manner [28]. SAAs can have a wide range of structural diversity as a

Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity

• Nisachon Khunnawutmanotham,
• Nitirat Chimnoi,
• Arunee Thitithanyanont,
• Patchreenart Saparpakorn,
• Kiattawee Choowongkomon,
• Pornpan Pungpo,
• Supa Hannongbua and
• Supanna Techasakul

Beilstein J. Org. Chem. 2009, 5, No. 36, doi:10.3762/bjoc.5.36

• , Ubonratchathani 34190, Thailand 10.3762/bjoc.5.36 Abstract Ten dipyridodiazepinone derivatives were synthesized and evaluated for their anti HIV-1 reverse transcriptase activity against wild-type and mutant type enzymes, K103N and Y181C. Two of them were found to be promising inhibitors for HIV-1 RT. Keywords

• : AIDS; anti HIV-1 RT; dipyridodiazepinone; nevirapine; synthesis; Introduction Dipyridodiazepinone nevirapine (1) [1] (Figure 1) is a potent non-nucleoside inhibitor of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) and is approved as a therapeutic agent for the treatment of AIDS

• ][5][6][7][8]. On the basis of molecular modeling analysis on the wild-type (WT) and Y181C HIV-1 RT, it was found that the dipyridodiazepinone derivatives containing an unsubstituted lactam nitrogen and a 2-chloro-8-arylthiomethyl moiety, when compared with 9 [4] (Figure 2) as reference, are effective

A short stereoselective synthesis of (+)-(6R,2′S)-cryptocaryalactone via ring- closing metathesis

• Palakodety Radha Krishna,
• Krishnarao Lopinti and
• K. L. N. Reddy

Beilstein J. Org. Chem. 2009, 5, No. 14, doi:10.3762/bjoc.5.14

• ], they inhibit HIV protease [8][9], induce apoptosis [10][11][12][13][14][15], and have even proved to be antileukemic [16]. At least some of these pharmacological effects may be related to the presence of the conjugated double bond, which acts as a Michael acceptor [17][18][19][20][21][22][23]. One of

Synthesis of crispine A analogues via an intramolecular Schmidt reaction

• Ajoy Kapat,
• Ponminor Senthil Kumar and
• Sundarababu Baskaran

Beilstein J. Org. Chem. 2007, 3, No. 49, doi:10.1186/1860-5397-3-49

• considered to be lead drug molecules in the treatment of metabolic diseases such as diabetes, cancer and HIV infection. [5][6][7] The alkyl indolizidine alkaloids, also called gephyrotoxins, are well-known for their ability to function as non-competitive blockers of neuromuscular transmission [2] by

N-1 regioselective Michael- type addition of 5-substituted uracils to (2-hydroxyethyl) acrylate

• Sławomir Boncel,
• Dominika Osyda and
• Krzysztof Z. Walczak

Beilstein J. Org. Chem. 2007, 3, No. 40, doi:10.1186/1860-5397-3-40

• -isopropyl-6-benzyluracyl) are in the third stage of clinical testing for their inhibition of HIV-1 reverse transcriptase.[3] Others, like acyclovir or gancyclovir are in clinical use.[4] Cidofovir, (S)-3-hydroxy-2-phosphonomethoxypropyl cytosine, is an acyclonucleoside that possesses broad-spectrum activity

Reaction of benzoxasilocines with aromatic aldehydes: Synthesis of homopterocarpans

• Míriam Álvarez-Corral,
• Cristóbal López-Sánchez,
• Leticia Jiménez-González,
• Antonio Rosales,
• Manuel Muñoz-Dorado and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2007, 3, No. 5, doi:10.1186/1860-5397-3-5

• potential anti-HIV. [15] A theoretical study of their structure has also been published. [16] Here we describe a concise and convergent approach to this skeleton (1) based on a Sakurai condensation between a benzoxasilocine (2) and a protected ortho-hydroxybenzaldehyde (Scheme 1). Results and discussion

An efficient synthesis of tetramic acid derivatives with extended conjugation from L-Ascorbic Acid

• Biswajit K. Singh,
• Surendra S. Bisht and
• Rama P. Tripathi

Beilstein J. Org. Chem. 2006, 2, No. 24, doi:10.1186/1860-5397-2-24

• tetramic acid antibiotics with dienyl or polyenyl units are shown in Figure 1. 3-Acetyl tetramic acid derivatives are known to act as anti-HSV and anti-HIV agents with potent tyrosine phosphatase inhibitory activities. [10][11][12] The distinct structural features and pharmacological properties of tetramic

• and are potentially new tuberculosis drugs. 5-Alkenyl tetramic acids, being structurally similar to thiolactomycins, possess anti-HCV and anti-HIV activities [34][35] and are likely to yield new antitubercular prototype compounds active against tuberculosis in HIV cases. We have developed a one-pot

One-pot synthesis of novel 1H-pyrimido[4,5-c][1,2]diazepines and pyrazolo[3,4-d]pyrimidines

• Dipak Prajapati,
• Partha P. Baruah,
• Baikuntha J. Gogoi and
• Jagir S. Sandhu

Beilstein J. Org. Chem. 2006, 2, No. 5, doi:10.1186/1860-5397-2-5

• -c]pyridazine-5,7-dione), inhibits the growth of Pseudomonas 568 and also binds to herring sperm DNA.[7] However, until the emergence of HEPT[8] as a potent and selective inhibitor of HIV-1, no attention was given to the synthetic manipulation at the 6-position of uracils. Also the synthetic

• compounds of biological importance including anti-tumor antibiotics and inhibitors of HIV-1 transcriptase.[30] New methods continue to appear in the literature describing the synthesis of novel benzodiazepine analogues[31], and emphasis is placed on the alteration and replacement of benzene ring with a

Stereoselective α-fluoroamide and α-fluoro- γ-lactone synthesis by an asymmetric zwitterionic aza-Claisen rearrangement

• Kenny Tenza,
• Julian S. Northen,
• David O'Hagan and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2005, 1, No. 13, doi:10.1186/1860-5397-1-13

• intermediate in the synthesis of the anti-HIV nucleoside β-FddA1 6. [17][18] Results and discussion In order to undertake the appropriate zwitterionic aza-Claisen rearrangement reactions an efficient method for the production of the α-fluoro acid chloride substrates was required. A number of routes to 2