Absolute stereochemistry, definition

The complete structure of schelhammerine (except for stereochemistry at C-2 and C-5) was deduced as 80a from a careful analysis of its 100-MHz NMR spectrum, with the aid of decoupling experiments. Values of 5.0 Hz for J3,4eq and 3.2 Hz for /3>4ax suggested that the proton at C-3 was equatorial but a value of 3.0 Hz for J2A did not allow definitive assignment of the stereochemistry at C-2, although it suggested that the proton at C-2, was also equatorial. The absolute stereochemistry (as shown in 80a) was established by X-ray analysis of schelhammerine hydrobromide (92). 

Lipoxygenase enzymes are known to oxidize arachidonic acid at six possible positions. The chemical requirement for this oxidation (Eq. 4.1) appears simply to be a skipped cis diene which can produce (via the enzyme) a stabilized allylic radical, which then traps molecular oxygen to form a conjugated cis-trans diene hydroperoxide. Chart 4.1 shows the six possible mono-oxidation products as members of the HETE family. All of these compounds have been shown to be natural products. Only in the cases of 8 and 9 HETEs is the absolute stereochemistry not definitively known. Nevertheless, it is speculated that 8-HETE has the alcohol in the (5)-configuration and 9-HETE is of the (R) absolute... 

The total synthesis of complex natural products offers challenges in the construction of the carbon framework, adjustment of the oxidation pattern, control of relative stereochemistry and control of absolute stereochemistry. While all of these areas offer exciting opportunities, the last remains the least considered and most perplexing in developing particular synthetic strategy. To a very large extent, total synthesis of natural products still implies the synthesis of a racemate which, by definition, contains only 50% of the natural product and may be resolved at the end or along the way. 

The spectral information reduced the number of possible structures to six, and although biogenetic arguments (see Section VII) led to a clear preference for structure 52 (without stereochemical details), no definitive evidence which would distinguish this structure from the other possibilities was available. Consequently, a single crystal X-ray structure analysis was undertaken, and this established the structure and stereochemistry of Sceletium alkaloid A4 as 52 (55, 38). Because the X-ray structure analysis was effected by the nonheavy-atom direct-methods approach, the absolute stereochemistry was not provided. Structure 52 is represented rather than its mirror image simply because it corresponds to the absolute stereochemistry of the alkaloids of the mesembrine series. The chemical correla-... 

The total synthesis of cytostatin (58), an antitumor agent belonging to the fostriecin family of natural products has been described in detail. The definitive assignment of the relative and absolute stereochemistry of cytostatin and that of each of its Cio-Cn stereoisomers were established. It was found that each element of... 

The structures and the absolute configuration of these alkaloids have been firmly established by chemical and physical methods since that time. The work which has been carried out in this field led to the structural assignment of a new alkaloid, habranthine (155), to the definition of the stereochemistry of chlidanthine (152), and to the synthesis of galanthamine-type derivatives through several approaches. 

The synthesis of the models shown above acquired additional meaning from the absolute novelty of the stereochemistry problems which became available to experimental studies. While it is premature to make definite suggestions about the peculiarities of the chemistry of compounds having topological bonds, the uniqueness of their structure seems to guarantee that a number of non-trivial phenomena, such as unusual chelating properties, regulated catalytic activity, etc., will be discovered in this field. ... 

As was mentioned above these conclusions were strikingly confirmed by a definitive X-ray crystallographic study of the structure of villalstonine this investigation also established that the relative stereochemistry is as shown in XIV 31). If the assumption is made that villalstonine possesses the same absolute configuration at C-15 and C-15 as all the yohimbine and heteroyohimbine alkaloids, then XIV also represents the absolute configuration of the molecule. 

---