Examination of nature's favorite molecules reveals a striking preference for making carbon-heteroatom bonds over carbon-carbon bonds-surely no surprise given that carbon dioxide is nature's starting material and that most reactions are performed in water. Nucleic acids, proteins, and polysaccharides are condensation polymers of small subunits stitched together by carbon-heteroatom bonds. Even the 35 or so building blocks from which these crucial molecules are made each contain, at most, six contiguous C-C bonds, except for the three aromatic amino acids. Taking our cue from nature's approach, we address here the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C-X-C), an approach we call "click chemistry". Click chemistry is at once defined, enabled, and constrained by a handful of nearly perfect "spring-loaded" reactions. The stringent criteria for a process to earn click chemistry status are described along with examples of the molecular frameworks that are easily made using this spartan, but powerful, synthetic strategy.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3773%2820010601%2940%3A11%3C2004%3A%3AAID-ANIE2004%3E3.0.CO%3B2-5

Click Chemistry: Diverse Chemical Function from a Few Good Reactions.

Betrachtet man die in der Natur am haufigsten vorkommenden Verbindungen, so fallt auf, dass die Bildung von Kohlenstoff-Heteroatom-Bindungen gegenuber der von Kohlenstoff-Kohlenstoff-Bindungen deutlich bevorzugt ist Da zum einen Kohlendioxid die Basisverbindung der Natur ist und andererseits das Medium naturlicher Reaktionen zumeist Wasser ist, uberrascht dies sicherlich nicht Nucleinsauren, Proteine und Polysaccharide sind polymere Kondensationsprodukte kleiner Untereinheiten, die durch Kohlenstoff-Heteroatom-Bindungen verknupft sind Sogar die etwa 35 Baueinheiten, aus denen diese essentiellen Verbindungen bestehen, enthalten nicht mehr als sechs aufeinander folgende C-C-Bindungen, sieht man einmal von den drei aromatischen Aminosauren ab Mit der Natur als Vorbild richteten wir unser Interesse auf die Entwicklung leistungsfahiger, gut funktionierender und selektiver Reaktionen fur die effiziente Synthese neuartiger nutzlicher Verbindungen sowie kombinatorischer Bibliotheken mittels Heteroatomverknupfungen (C-X-C) Diese Synthesestrategie nennen wir „Click-Chemie“ Click-Chemie ist durch eine Auswahl einiger weniger nahezu idealer Reaktionen charakterisiert, mit all ihren Grenzen und Moglichkeiten In diesem Beitrag werden zum einen die strengen Kriterien, die Reaktionen erfullen mussen, um die Bezeichnung „Click-Chemie“ zu verdienen, definiert, zum anderen werden Beispiele fur molekulare Strukturen gegeben, die mit dieser spartanischen, aber dennoch leistungsfahigen Synthesestrategie leicht hergestellt werden konnen

Click-Chemie: diverse chemische Funktionalität mit einer Handvoll guter Reaktionen

Claisen rearrangement over the past nine decades.

Recent developments in the stereoselective synthesis of α-aminoacids

(1990). The Shikimate Pathway — A Metabolic Tree with Many Branche. Critical Reviews in Biochemistry and Molecular Biology: Vol. 25, No. 5, pp. 307-384.

The shikimate pathway―a metabolic tree with many branches

Bromination of epi-inosamine-2 in a mixture of acetyl bromide and acetic anhydride afforded 1, 5-dibromo-1, 5-dideoxy-rac-inosamine-6. From this compound, two hitherto unknown inosadiamines: myo-inosadiamine-2, 4 and muco-inosadiamine-2, 3, were obtained by displacement of the bromo groups by azide ions, followed by hydrogenation. The configurations of the new compounds obtained were established by the nuclear magnetic resonance spectra.

Aminocyclitols. XVI. A Synthesis and Configurational Study of Dibromo-dideoxyinosamine

Practical synthesis of optically pure 3,4-epoxy-5-methyldihydro-2(3H)-furanones from d-xylose by regio- and stereo-selective functionalization

The reaction of l,2-O-cyclohexylidene-myo-inositol (1a) with 1.5 equiv. of benzoyl chloride below 0°C gave 3-O-benzoate (2a) predominantly in 40% yield, together with easily separable 3,6-di-O-benzoate (3a) in 2.5% yield. Selective sulfonylation of 2a gave three new O-p-tolylsulfonyl-myo-inositols (the 4,6- (8a), 4,5- (9a), and 4,5,6-p-toluenesulfonates (10)). From 3a, two O-p-tolylsulfonyl derivatives (5- (15a) and 4,5-p-toluenesulfonates (16)) were obtained. The relative reactivities, toward benzoylation, of the hydroxyl groups of 1a were shown to be almost similar to those observed in tosylation. The p-tolylsulfonyloxy function on C–5 of 10 was found to be readily displaced preferentially by chloride ion.

Inositol Derivatives. V. Selective Benzoylation of 1,2-O-Cyclohexylidene-myo-inositol and Preparation of New O-p-Tolylsulfonyl-myo-inositols

Hydrazinolysis of DL-1,4-dibromo-1,4-dideoxy-chiro-inositol (3a), followed by catalytic hydrogenation and acetylation, afforded di-N-acetyl-tetra-O-acetyl-neo-inosadiamine-1,3 (6a) and -scyllo-inosadiamine-1,3 (7) in 18% and 24% yields, respectively. From the intact hydrazinolyzate of 3a, two new stereoisomeric 1,3-biimino-1,3-dideoxy-inositols (4a and 5a) could be isolated, and their structures were established by correlating to the corresponding inosadiamines. A similar hydrazinolysis of 3,6-di-O-p-tolylsulfonyl-muco-inositol (12) gave sole crystalline 1,3-biimino compound (13a), whose structure was followed from its conversion into known di-N-acetyltetra-O-acetyl-myo-inosadiamine-4,6 (14). PMR spectra of four 1,3-biimino compounds were discussed.

Aminocyclitols. XXIX. Synthesis of Inosadiamines via 1,3-Biimino-1,3-dideoxy-inositols

Practical synthesis of ether-linked 5a¢-carbamaltose and -cellobiose, and the related carbadisaccharide starting from a sole condensate of the 1,2-anhydro-3-O-benzyl-4,6-O-benzylidene-5acarba-b-D-mannopyranose and methyl 2,3,6-tri-O-benzyl-a-D-glucopyranoside is described.

Synthesis of Building Blocks for Carba-oligosaccharides: 5a′-Carbamaltose and 5a′-Carbacellobiose, and 5a-Carba-β-d-mannopyranosyl-(1→4)-d-glucopyranose

Seiichiro Ogawa

Papers

Aminocyclitols. XVI. A Synthesis and Configurational Study of Dibromo-dideoxyinosamine

Practical synthesis of optically pure 3,4-epoxy-5-methyldihydro-2(3H)-furanones from d-xylose by regio- and stereo-selective functionalization

Inositol Derivatives. V. Selective Benzoylation of 1,2-O-Cyclohexylidene-myo-inositol and Preparation of New O-p-Tolylsulfonyl-myo-inositols

Aminocyclitols. XXIX. Synthesis of Inosadiamines via 1,3-Biimino-1,3-dideoxy-inositols

Synthesis of Building Blocks for Carba-oligosaccharides: 5a′-Carbamaltose and 5a′-Carbacellobiose, and 5a-Carba-β-d-mannopyranosyl-(1→4)-d-glucopyranose