LHASA program

Ott M. A., Noordik J. H. Long-Range Strategies in the LHASA Program The Quinone Diels-Alder Transform J. Chem. Inf. Comput. Sci. 1997 37 98 108 Keywords computer application, quinone Diels-Alder transformations... 

M.A. Ott and J.H. Noordik, Long-range strategies in the LHASA program the Quinone Diels-Alder transform. J. Chem. Inf. Comput. Sci., 37 (1997) 98-108. 

Let us consider the general principles of operation of the LHASA program in finding a synthetic pathway to polycyclic system. The program can be aimed by the chemist along two modes of search. The first mode of operation implies that... 

As a check on the effectiveness of the LHASA program, the authors performed an analysis on 14 polycyclic compounds for which a synthesis was already reported in the literature. In 10 of these cases, the LHASA program included in the set of the generated solutions the very synthetic schemes that had been successfully realized. 

As demonstrated above, the most efficient reactions in the construction of cyclic structures are those that lead to the formation of several bonds as the result of a single chemical operation. This consideration stimulated the development of an alternative version of the LHASA programs aimed at finding ways of dismantling target structures with the help of especially effective disconnec-... 

Retrosynthetic Analysis. An approach to computer-assisted synthesis design that starts with the products of a reaction or sequence of reactions and works backwards toward the reactants. An example program that implements retrosynthetic analysis is the LHASA program of E. J. Corey s group. 

Conformational Analysis for Six-Membered Rings in the LHASA Program... 

Figure 6 Incremental calculation scheme to predict destabilization energies ED in monoaxial substituted (a), 1,2-diequatorial substituted (b), and 1,3-diaxial substituted (c) cyclohexane chair conformations in the LHASA program.

These concepts were developed into the computer program SYNGEN147 (SYNthesis GENeration). As with Corey s LHASA program, inspection of the main principles of the program can offer useful information for a synthesis. It is emphasized that this section has only touched the surface of Hendrickson s detailed and comprehensive analysis. Once understood, any target can be analyzed in detail to provide a synthetic tree. 

The Diels-Alder reaction is one of the powerful reactions referred to by Corey in his LHASA program for synthesis (sec. 10.4.B). One of the powerful features of the Diels-Alder reaction is the stereochemical selectivity inherent to the cycloaddition and many examples exist in the total synthesis of natural products. ... 

Ease of Use and User Friendliness. The LHASA program displays a Sketch Pad screen and activates "Draw Mode." A large rectangular drawing area is surrounded by three menu areas and a message window at the bottom of the screen. Cursor movement is controlled using a mouse (or cursor keys). All other screens are accessible via the Sketch Pad menus. 

The LHASA program is exceedingly complex - about 400 subroutines, 30,000 lines of FORTRAN code and a data base of over 600 common chemical reactions. To describe it in detail is well beyond the scope of this paper. A general overview is relevant as it puts the functions of the data base in a reasonable perspective. Figure 1 shows a global view of LHASA. 

Fig. 9.9. Computer screen from the LHASA program showing a reaction step (with permission of LHASA UK Ltd). 

A. P, Johnson and C. Marshail, /. Chem. Inf Comput. Sci., 32,418 (1992). Starting Material Oriented Retrosynthetic Analysis in the LHASA Program. 2. Mapping the Starting Material and Target Structures. 

Corey et a/." have now applied the LHASA program to pre-evaluate the procedures required to arrive at the key simplifying disconnection in the annulation. 

This strategy has been incorporated into the LHASA program. LHASA finds the appropriate starting materials, then it determines the nature and the order of the reactions steps which are required and, finally, it elaborates the sequences by application of the transforms of the knowledge base. ... 

---