Synthesis of Aminocyclitol Antibiotics

Abstract

The first aminoglycoside antibiotic described was strepto mycin discovered by Waksman and coworkers in 1944, and, since then, remarkable development has been made in this field of antibiotics. The number of structurally elucidated aminocyclitol antibiotics of microbial origin is now about one hundred. Various antibiotics among them have been utilized for chemothera py, being especially useful for treatment of serious Gram-nega tive infections.The study of aminocyclitol antibiotics and other sugar -containing antibiotics has provided some fascinating and challenging problems in the field of carbohydrate chemistry. Structural, stereochemical and conformational studies of this group of antibiotics have been expedited particularly by means of proton n.m.r. spectroscopic techniques. For instance, the glycosidic linkage between streptose and streptidine was deter mined to be α-L in 1965 by Rinehart and McGilveray (1) on the basis of n.m.r. spectral studies. Recently, 13 C-n.m.r. spectros copy and mass spectroscopy have greatly contributed to the advances in this field.In addition, it should be noted that Reeves method (2,3) for determination of the conformations of pyranosides has greatly contributed to the advances in this field. Reeves method is concerned with the stereochemical relationship between adjacent hydroxyl groups on pyranosides and based on the difference in optical rotations between solutions of sugar derivatives in cuprammonium solution and water. For instance, the absolute configuration of unsymmerically substituted 2-deoxystreptamine portion of deoxystreptamine-containing antibiotics was first established by application of this method, as reported by Rinehart and Hichens (j4) in 1963. We successfully modified this method by use of a solution of tetraamminecopper(II) sulfate instead of the cuprammonium solution (5). With this reagent Cu(II)-complexing occurs between vicinal trans-equatorial amino and hydroxyl groups, but not between vicinal trans-equatorial hydroxyl groups. This affords useful information concerning the 0-8412-0554-X/80/47-125-015$06.75/0

Συμβολη Στην Ημισυνθεση Αμινογλυκοζιτικων Αντιβιοτικων

“…Τα περισσότερα απ'αυτά παράγονται από είδη που ανήκουν στους στρεπτομύκητες, τα μικρομονόσπορα, τους βακΐλους ακόμα και τις ψευδομονάδες (πίνακας 2). Η βακτηριακή δραστικότητα εναντίον των αερόβιων βακϊλων, η κάλυψη στο περιβάλλον των ψευδομονάδων και η αντιφυματιακή δράση αποτελούν τους τρεις σημαντικότερους λόγους για τη χρησιμοποίηση τους 16 . Η σχέση δόσης -τοξικότητας από την άλλη πλευρά είναι ο κύριος παράγοντας που περιορίζει τη χρήση τους και οδηγεί στην επιλογή άλλων κατηγοριών αντιβιοτικών 17 .…”