6.4. Polyynes 3123 6.5. Using R-Hydroxy Stannanes 3124 6.6. Using the Hurtley Reaction 3124 6.7. Using a Methylenation Reaction 3125 7. Conclusions and Future Prospects 3125 8. Uncommon Abbreviations 3125 9. Acknowledgments 3125 10. Note Added in Proof 3125 11. References 3126 * Authorstowhomcorrespondenceshouldbeaddressed(evano@chimie.uvsq.fr, nicolas.blanchard@uha.fr). † Université de Versailles Saint Quentin en Yvelines. ‡ Université de Haute-Alsace. Chem. Rev. 2008, 108, 3054–3131 3054

Copper-mediated coupling reactions and their applications in natural products and designed biomolecules synthesis.

Cleḿence Queffeĺec,† Marc Petit,†,‡ Pascal Janvier,† D. Andrew Knight, and Bruno Bujoli*,† †LUNAM Universite,́ CNRS, UMR 6230, Chimie Et Interdisciplinarite:́ Synthes̀e Analyse Modeĺisation (CEISAM), UFR Sciences et Techniques, 2, rue de la Houssinier̀e, BP 92208, 44322 NANTES Cedex 3, France ‡Universite ́ Pierre et Marie Curie (UPMC), CNRS, UMR7201, Institut Parisien De Chimie Molećulaire (IPCM), 4 place Jussieu, 75252 Paris Cedex 05, France Chemistry Department, Florida Institute of Technology, 150 West University Boulevard, Melbourne, Florida 32901, United States

Surface modification using phosphonic acids and esters.

To create a drug, nature's blueprints often have to be improved through semisynthesis or total synthesis (chemical postevolution). Selected contributions from industrial and academic groups highlight the arduous but rewarding path from natural products to drugs. Principle modification types for natural products are discussed herein, such as decoration, substitution, and degradation. The biological, chemical, and socioeconomic environments of antibacterial research are dealt with in context. Natural products, many from soil organisms, have provided the majority of lead structures for marketed anti-infectives. Surprisingly, numerous "old" classes of antibacterial natural products have never been intensively explored by medicinal chemists. Nevertheless, research on antibacterial natural products is flagging. Apparently, the "old fashioned" natural products no longer fit into modern drug discovery. The handling of natural products is cumbersome, requiring nonstandardized workflows and extended timelines. Revisiting natural products with modern chemistry and target-finding tools from biology (reversed genomics) is one option for their revival.

Antibacterial Natural Products in Medicinal Chemistry—Exodus or Revival?

Large-Scale Applications of Amide Coupling Reagents for the Synthesis of Pharmaceuticals

Biodiesel fuel, a promising alternative diesel fuel produced by a catalytic transesterification of vegetable oils, has become more attractive recently because of its environmental concerns and the fact that it is made from renewable resources. In this work, the transesterification of soybean oil with methanol has been studied in a heterogeneous system, using alumina loaded with potassium iodide as a solid base catalyst. After loading KI of 35 wt.% on alumina followed by calcination at 773 K for 3 h, the catalyst gave the highest basicity and the best catalytic activity for this reaction. The catalysts were characterized by means of XRD, IR, SEM and the Hammett indicator method. Moreover, the dependence of the conversion of soybean oil on the reaction variables such as the catalyst loading, the molar ratio of methanol to oil and the reaction time was studied. The conversion of 96% was achieved under the optimum reaction conditions. Besides, a correlation of the catalyst activity for the transesterification reaction with its basicity was proposed.

Alumina-supported potassium iodide as a heterogeneous catalyst for biodiesel production from soybean oil

A series of A-ring heterocyclic steroids has been prepared and tested for inhibition of rat prostatic steroid 5 alpha-reductase in vitro. Strikingly high inhibitory activity was found with a group of 17 beta-substituted 4-methyl-4-aza-5 alpha-androstan-3-ones. These compounds were prepared from 3-keto-delta 4-precursors by oxidative (O3 or NaIO4-KMnO4) A-ring cleavage followed, in turn, by ring closure with an amine and hydrogenation over platinum catalyst. Other A-ring azasteroids were made by Beckmann rearrangement of oximes of 2-oxo-A-nor, 3-oxo- and 4-oxo-5 alpha-androstanes. An A-nor-2-oxo-3-azasteroid was prepared by oxidative decarbonylation of a precursor 2,3-dioxo-4-azasteroid with m-chloroperbenzoic acid. A-ring modifications of the 4-azasteroids included delta 1-unsaturation, 2- and 4-substituents, and 3-carbonyl replacements. Side chains at the 17-position were varied with an emphasis on carboxylate derivatives (salts, esters, and amides).

Azasteroids as inhibitors of rat prostatic 5 alpha-reductase.

A new general method for preparation of N-methoxy-N-methylamides. Application in direct conversion of an ester to a ketone

Preparation of (4-Amino-1-Hydroxybutylidene)bisphosphonic Acid Sodium Salt, MK-217 (Alendronate Sodium). An Improved Procedure for the Preparation of 1-Hydroxy-1,1-bisphosphonic Acids

An improved process is described for the preparation of 4-amino-1-hydroxybutylidene-1,1-bisophosphonic acid (ABP) or salts thereof which comprises: (a) reacting 4-aminobutyric acid with a mixture of phosphorous acid and PCl3 in the presence of methanesulfonic acid; (b) contacting the mixture from Step (a) with an aqueous hydrolysis mixture, wherein the pH is maintained in the range of 4 to 10 during the contacting; and (c) recovering said 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid or salts thereof.

Process for preparing 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (ABP) or salts thereof

4-Aza-17-substituted-5a-androstan-3-ones and their A-and D- homo analogs of the formula:
 where Formula (I) may also have the structure of partial Formulas (II) and-or (III); wherein,
 A is
 (1) - CH 2 - CH 2 -; (2)-CH=CH-; (3)
 or (4)
 B is
 where R 1 is,
 (a) hydrogen; (b) methyl or ethyl; (c) ethenyl; (d) ethynyl; (e) NR 2 R 3 where R 2 and R 3 are hydrogen or methy : (f) cyano; or (2)
 where X ⊖ is any anion and R 4 is,
 (a) OR 5 where R 5 is C 1-4 alkyl; or (b) NR 6 R 7 , where R 6 and R 7 are hydrogen or methyl; R' is hydrogen or methyl; R" is hydrogen or β-methyl; R"' is B-methyl or hydroxy; Z is(1) oxo;
 (2) β-hydrogen and a-hydroxy; or a-hydrogen or a-hydroxyl and (3) (Y) n 0 where n = 0 or 1, Y is a straight or branched hydrocarbon chain of 1 to 12 carbon atoms and
 Q is
 (a) 0 
C - R 8 , where R 8 is,
 (i) hydrogen, (ii) hydroxyl, (iii) C 1-4 alkyl (iv) NR 9 R 10 , where R 9 and R 10 are each independently selected from hydrogen, C 1-4 straight or branched chain alkyl, C 3-6 cycloalkyl, phenyl; or R 9 and R'° taken together with the nitrogen to which they are attached represent a 5-6 membered saturated ring comprising up to one other heteratom selected from oxygen and nitrogen. (v) OR", where R" is M, where M is hydrogen or alkali metal, or C 1-18 straight or branched chain alkyl; benzyl; or (b) OR' 2 , where R 12 is,
 (i) C 1-20 alkylcarbonyl, (ii) phenyl C 1-6 alkylcarbonyl, (iii) C 5-10 cycloalkylcarbonyl, (iv) benzoyl, or (v) C 1-8 alkoxycarbonyl; (4)
 where the dashed bond replaces the 17a hydrogen; (5)
 where R" is,
 (a) C 1-12 alkyl; or (b) NR 9 R 10 ; (6) cyano; or 
(7) tetrazolyl; 
and pharmaceutically acceptable salts of the above compounds; active as testosterone 5a reductase inhibitors, and thus useful topically for treatment of acne, seborrhea, female hirsutism and male pattern baldness, and systemically in treatment of benign prostatic hypertrophy, breast carcinoma, and prostate carcinoma.

4-aza-17-substituted-5-alpha-androstan-3-one, their a and d homo analogs, process for their preparation and pharmaceutical compositions containing them

Ronald B. Jobson

Papers

Azasteroids as inhibitors of rat prostatic 5 alpha-reductase.

A new general method for preparation of N-methoxy-N-methylamides. Application in direct conversion of an ester to a ketone

Preparation of (4-Amino-1-Hydroxybutylidene)bisphosphonic Acid Sodium Salt, MK-217 (Alendronate Sodium). An Improved Procedure for the Preparation of 1-Hydroxy-1,1-bisphosphonic Acids

Process for preparing 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (ABP) or salts thereof

4-aza-17-substituted-5-alpha-androstan-3-one, their a and d homo analogs, process for their preparation and pharmaceutical compositions containing them