Thermolysis of 17 proceeded smoothly to afford the thioester 18 (98% yield) via the expected 3,3-sigmatropic rearrangement shown in Scheme 11. Exposure of thio imidazolide 18 to catalytic amounts of NaSMe in CH2Cl2 in the presence of excess EtSH led to the rather labile thiol 19 (95% crude yield), which was reacted immediately with acid chloride 4 (1.3 equiv) in the presence of DMAP-Et3N to afford coupling product 20 (80% yield based on thiol) (Scheme V). Controlled monodesilylation of 20 (1.0 equiv of nBu4NF) resulted in the formation of ketone 21, which was reduced selectively with K-selectride to afford hydroxy compound 22 in 75% overall yield from 20. Removal of all three triethylsilyl groups from 22 with HF-Pyr, followed by exposure of the resulting intermediate 23 to Et2NH in THF, led to the desired compound 24 in 87% overall yield. Finally, reduction of the oxime double bond in 24 with NaCNBH3 in MeOH at pH 3 furnished the targeted oligosaccharide 2, together with its C-4 isomer (90% yield, ca. 1:2 ratio). The two isomers were separated by flash column or preparative thin-layer chromatography (silica, ether-MeOH, 6:1), and the correct isomer (faster moving) was identified by 1H NMR studies and comparisons of the 1H NMR spectrum of its pentaacetate (25, Scheme V) with that of a closely related derivative derived from calicheamicin γI1 by degradation. The described chemistry is expected to facilitate molecular recognition experiments between calicheamicin oligosaccharide fragments, such as 2, and specific DNA strands, as well as pave the way for a total synthesis of the intact antibiotic (1). The terrestrial cyanophyte Scytonema mirabile (Dillwyn) Bornet (strain BY-8-1) produces a complex mixture of cytotoxins, the major and most potent one being tolytoxin. Interestingly, some of the cytotoxins in the lipophilic extract of this alga show marginal solid tumor selectivity at the cellular level in the Corbett assay. We report here the total structures of tantazoles A (1), B (2), F (3), and I (4), representatives of an unusual class of alkaloids that exhibit murine solid tumor selective cytotoxicity. The freeze-dried cyanophyte was extracted with 70% ethanol in water, and the resulting extract was subjected to repeated reverse-phase (C-18) chromatography to give the tantazoles as amorphous white solids. During the purification of tantazole A (1) and tantazole I (4), extensive air oxidation of both compounds to the didehydro compound 5 occurred. Structure studies, therefore, were carried out on 5 first. A high-resolution EIMS of didehydrotantazole A (5) suggested the molecular formula C24H30O2N6S4. The 13C NMR spectrum showed 10 sp2 and 14 sp3 carbon signals, and the 1H NMR spectrum displayed signals for one amide proton, three isolated nonequivalent methylene groups, a methine proton, and five methyl groups. On the basis of these data and heteronuclear correlations from HMQC and HMBC experiments, partial structures for rings B-E and the sequence of rings A-E could be deduced, but an unequivocal structure for ring A was not possible. An INADEQUATE experiment on 5 that had been uniformly enriched with 13C to 82% and 15N to >90% allowed construction of the six contiguous-carbon units in the molecule, thus establishing the structure of ring A. A 1H-15N HMBC experiment permitted connection of these six units to the six nitrogens in 5. Tantazoles A (1) and I (4) were isolated in good yield by faster workup and storage of all chromatographic fractions under argon at -196 °C during isolation. NMR (1H, 13C, HMQC, and HMBC) and MS analysis established identical gross structures for 1 and 4. Tantazole B (2) exhibited a molecular ion peak in its EIMS corresponding to C25H32O2N6S4, differing from 1 by a methyl group on C-4 of ring D. Tantazole F (3) showed a molecular formula C24H32O2N6S4, with a thiazoline methine located in ring B. CD spectra indicated tantazoles A, B, and F have the same relative and absolute stereochemistry (R at all chiral centers), while tantazole I (4) differs in stereochemistry at C-4 of ring D (S). Acid hydrolysis of compounds 1-5, followed by derivatization, afforded 2 equiv of 6 and 1 equiv of 7 from 1, 4, and 5, 4 equiv of 6 from 2, and 3 equiv of 6 and 1 equiv of 8 from 3. The quantitative CD spectra of 6 isolated from hydrolysates were identical, indicating all 4 methylthiazoline units have the same absolute stereochemistry (R). Compound 8 was identified as L-R by CD comparison with synthetic standards. The absolute configurations of all four chiral centers in tantazoles A (1), B (2), and F (3) and rings B, C, and E in tantazole I (4) are R; the absolute configuration of C-4 in ring D in tantazole I (4) is S. Recently we reported a second-generation synthesis of (-)-paspaline (1), the simplest member of a family of architecturally novel indole diterpenes. Central to the former was the development of a unified strategy, designed to encompass this entire class of fungal metabolites which now include (+)-paspalicine (2), (+)-paspalinine (3), and (+)-paxilline (4), using tricyclic ketone (-)-5 [9.4% overall yield from (+)-Wieland-Miescher ketone] as a prospective common intermediate containing the critical C(12b,12c) vicinal quaternary centers. In this communication we demonstrate the viability of this unified strategy with the first total syntheses of (+)-paspalicine (2) and (+)-paspalinine (3). Importantly, the potent tremorgen (+)-paspalinine represents the first biologically active indole diterpene to yield to total synthesis. Contrast with the paspaline venture (indole incorporated late), our point of departure for paspalicine and paspalinine entailed conversion of (-)-5 to (+)-7 via the Gassman indole protocol (46% overall yield), containing the ABCDE-ring system. Installation of rings F and G involved alkylation of (+)-7's thermodynamic enolate with epoxide (-)-17 (prepared in six steps via Sharpless asymmetric epoxidation, protection, and diastereoselective methylenation) using the Stork metalloenamine protocol (50% yield), followed by migration of the P,γ-olefin to conjugation to give (+)-8. Acetylation of the secondary hydroxyl, hydrazone hydrolysis, and acid-promoted deketalization/cyclization afforded advanced intermediate (+)-10. Acetate removal and Moffatt oxidation provided (+)-12 (and minor (+)-2), which was fully converted to (+)-paspalicine using the Clive modification of Grieco's rhodium chloride protocol. Synthetic (+)-2 was identical in all respects (500-MHz 1H NMR, 125-MHz 13C NMR, IR, MS, X-ray, mp, mmp, specific rotation) with an authentic sample kindly provided by Professor Arigoni. Further oxidation at C(4b) furnished (+)-paspalinine (3).