Conica can: The In(OTf)3‐catalyzed cyclization of nitrogen‐ and oxygen‐tethered acetylenic malonic esters gives five‐ to seven‐membered heterocycles in moderate to excellent yields (see scheme; Tf=trifluoromethanesulfonyl). The asymmetric synthesis of (−)‐salinosporamide A illustrates the synthetic utility of the method.

Die In(OTf)3‐katalysierte Cyclisierung von Malonsäureestern, die über Stickstoff‐ oder Sauerstoffatome mit acetylenischen Dreifachbindungen verbrückt sind, führt in mäßigen bis ausgezeichneten Ausbeuten zu fünf‐ bis siebengliedrigen Heterocyclen (siehe Beispiel; Tf=Trifluormethansulfonyl). Die asymmetrische Synthese von (−)‐Salinosporamid A illustriert das Anwendungspotenzial der Methode.

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+)-Fostriecin and (+)-phoslactomycin B, which are potent and selective inhibitors of protein phosphatase, were synthesized by a highly enantio-and stereoselective approach that enabled us to prepare all possible isomers at both the C11 secondary alcohol position and the D 12 -double bond.The soil bacteria species Streptomyces produce a series of structurally novel antifungal and antitumor antibiotics that include fostriecin, 1 PD113,271, 1 the phoslactomycins A-F and I, 2 the phosphazomycins C 1 and C 2 , 3 and the leustroducsins A-C and H. 2e,4 These compounds are highly potent and selective inhibitors of protein serine/threonine phosphatase 2A, which may account for their antitumor activity. 5,6 Because of their intriguing molecular architectures and their potential as a lead compounds for anticancer drugs, as well as their importance as biological tools, this class of compounds has attracted much attention in the chemical and biological communities. 7 As a result, there have been a number of formal and total syntheses of fostriecin, 5a,8,9 PD113,271, 10 leustroducsin B, 11,12 and phoslactomycin A and B, 13 including ours. Here, we describe details of our total syntheses of (+)-fostriecin (1) 9f and (+)-phoslactomycin B (2); 13c the methods used also enabled us to prepare various analogues of these compounds.The close structural similarity between (+)-fostriecin (1) and (+)-phoslactomycin B (2) allowed us to devise a common synthetic plan, which is illustrated in Scheme 1. We envisaged ynone 7 as a precursor to make our approach flexible. We expected that the advanced intermediate 3, as well as its stereoisomers 4, 5, and 6, would each be available from 7 by a combination of stereoselective formation of the (E)-or (Z)-iodoenone 14 and C9-OH directed anti-or syn-selective reduction. 15 To access 7, we envisaged an approach from alcohol 8 involving ring-closing metathesis 16 and Sharpless asymmetric dihydroxylation, 17 both of which were thought to be challenging in terms of selectivity because of the possibility of reaction occurring at several sites. In addition, the key issues to be addressed for the synthesis of 2 were stereoselective construction of the C4 asymmetric center and the installation of the C8 asymmetric quaternary center along with its aminoethyl substituent. Scheme 1 Retrosynthetic analysis of fostriecin and phoslactomycin BThe synthesis of fostriecin (1) began with the stereoselective preparation of trienol 12 (Scheme 2). 2,3-Dihydrofuran was first converted into the (3E)-4-(tributylstannyl)pent-3-en-1-ol with complete E-selectivity by means of Aldisson's procedure. 18 (3E)-4-(Tributylstannyl)pent-3-en-1-ol was subjected to p-methoxybenzylation to give the ether 9, which was iodinated to give alkenyl iodide 10. Heck reaction 19 of the iodide 10 with acrolein, gave the aldehyde 11. Brown's asymmetric allylation 20 of 11 gave alcohol 12 in good yield. The optical purity of 12 was not determined at this stage because of its instability both under the conditions for HPLC analysis on a chiral column...