Solid-Phase Organic Syntheses

Instructions for Proposal Submission

20 Dec 98

Solid-Phase Organic Syntheses, a new book series published by John Wiley and Sons, is an homage to the famous Organic Syntheses series created at the University of Illinois in the 1940's. The purpose of Solid-Phase Organic Syntheses (SPOS) is to provide solid-phase synthesis procedures that are repeatable and that lab scientists will have a desire to repeat.

Some SPOS procedures will describe library synthesis. Others will not. All submissions must be submitted first as Proposals in outline form and reviewed by Advisory Board members to determine Significance. Proposals should include a reaction scheme and all of the reagents that will be used. Upon acceptance of the Proposal, the author will be invited to make a full submission according to SPOS policies. The Editorial office will solicit a lab willing to serve the checking function, and the submission will be sent to that lab. The Checker will submit their addendum to the submission, together with an evaluation of the technical merit of the submission. Only submissions meeting both the Significance and the Technical Merit evaluations will be included in the series.

SPOS solicits work in the following three areas: (a) synthetic routes leading to libraries with at least two diversity-introducing steps, (b) linker strategies (cleavage), and (c) methods for the preparation of broadly- useful synthesis resins. Solid-phase quench methodologies for library generation, while of obvious value, are not considered appropriate for this series; however, the preparation of the resins themselves may be.

The final size of reported libraries should be small enough so that EVERY product can be characterized and the yield reported. While the Journal of Combinatorial Chemistry recently struggled with and established guidelines for percent success and percent confidence, this is not SPOS' role. Anyone repeating an SPOS library synthesis must have confidence that the products they obtain will be correct.

A route with two diversity steps will use at least five reagents in each step (25 member library). A route with three diversity steps will use at least three reagents in each step (27 member library). No routes will use less than three reagents in any diversity step.

The diversity inputs used should help to demonstrate the range of reagents that can be used. It is entirely acceptable for a submitter to choose the necessary 3-5 reagents from a much larger library that they have synthesized previously. Evaluation of the diversity of reagents used will be an important component of the review process.

The identity of every product will be confirmed by use of NMR and mass spectroscopy using the crude products; authors will submit this data with the manuscript as Supplementary Material for use by the Checkers.

An accurate yield for every product will be determined using either: (a) NMR integration of samples containing an internal standard of known concentration (simplest method); or, (b) purification followed by weight determination. Yield will be calculated based on actual amount of cleaved product divided by actual (or theoretical) loading of the support x 100%.

The problem of solid-phase support variability from supplier to supplier to batch to batch is unique to solid-phase synthesis. Reactions that succeed on one batch of support can fail on another. To the present time, there is no certain way to avoid this problem. The manufacturer and batch numbers of supports used should be included in the General Section of the Experimental Method. Furthermore, Submitters are urged to retain a sample of the support utilized in the event that its use is required.

Submitters are strongly encouraged to describe their experience in the success AND FAILURE of diversity inputs, solvents, and other matters that would assist others in repeating or expanding on the reported library synthesis. Such material will be included in the Discussion section of a submission.

The principal author is asked to prepare a brief (1-2 pages) description of the proposed manuscript. Be sure that the reaction scheme and structures of all diversity reagents are included.

The Proposal should be sent to the Editorial Office, currently: