Synthesis of the azaspiracid-1 trioxadispiroketal

The de novo analysis, design, and synthesis of the azaspiracid-1 trioxadispiroketal system is described. A revised structural model was developed on the basis of an independent analysis of the NMR spectral data of the natural product that fit all of the data and the thermodynamically favored spiroketal paradigm. This model was then tested via synthesis using a novel trioxadispiroketalization process and supported by spectroscopic correlation.     

An iodoetherification-dehydroiodination strategy for the synthesis of complex spiroketals from dihydroxyalkene precursors

Dihydroxyalkenes or their monoprotected alcohol derivatives are transformed to 5,5- and 5,6-spiroketals through a sequence involving an initial iodocyclization, followed by a silver triflate mediated spiroketalization step on the derived hydroxy-iodoether.     

Synthesis of the ABCD and ABCDE ring systems of azaspiracid-1

The efficient syntheses of the ABCD ring system of the originally proposed structure of azaspiracid-1 and the ABCDE ring system of the revised structure of azaspiracid-1 containing the correct stereochemistry at C(6), C(10), C(13), C(14), C(16), C(17), C(19), C(21), C(22), C(24) and C(25) have been achieved.     

Synthesis of the spirastrellolide A trioxadispiroketal

[reaction: see text] The core trioxadispiroketal system representing C26-C40 of spirastrellolide A was assembled using a sequenced double-intramolecular hetero-Michael addition process.     

Synthesis of spiroketals under neutral conditions via a type III ring-rearrangement metathesis strategy

A conceptually novel approach to spiro- and dispiroketals of various ring-sizes under neutral conditions has been designed which complements the classical thermodynamically driven tactic. Key steps involved the formation of α-alkoxyfurans, their [4+2] or [4+3] cycloaddition reactions and the ring-rearrangement metathesis of the resulting oxabicycles.     

Synthesis of chiral subunits for macrolide synthesis: an efficient method for converting spiroketals into open-chain derivatives

An efficient method for the conversion of the spiroketals $\text{9}$, $\text{11}$ and $\text{15}$ into open-chain derivatives by thioketal exchange is reported.     

Synthesis of the C-1-C-28 ABCD unit of spongistatin 1

The synthesis of the C-1-C-28 ABCD fragment of spongistatin is described. Anti-selective boron-mediated aldol coupling of a CD spiroketal ketone fragment to an AB spiroketal aldehyde unit forms the desired C1-C28 advanced intermediate. Other features include the double conjugate addition of a dithiol to an ynone to generate the key beta-keto-dithiane unit required for the synthesis of the AB spiroketal fragment. [reaction: see text]     

Synthesis of electron deficient 5,6-aryloxy spiroketals

[reaction: see text] A strategy for the construction of electron deficient 5,6-aryloxy spiroketal is reported. The process should prove useful for the synthesis of natural products containing similar spiroketals. The strategy uncovers an unexpected rearrangement between ortho and para quinone spiroketals.     

Synthetic study of azaspiracid-1: synthesis of the EFGHI-ring fragment

Here, we report a synthesis of the lower half C21-C40 fragment of the shellfish toxin, azaspiracid-1. The C28-C40 fragment was synthesized by a coupling between the C28-C35 epoxide and the C36-C40 dithioacetal anion, followed by the HI-ring spiroaminal formation. An aldehyde corresponding to the C28-C40 fragment was then coupled with the C21-C27 allylic stannane by using InCl3. Finally, the FG-ring was constructed by HF.pyridine to accomplish the synthesis of the suitably protected C21-C40 fragment.     

Total synthesis and structural elucidation of azaspiracid-1. Final assignment and total synthesis of the correct structure of azaspiracid-1

The molecular structure of azaspiracid-1, a neurotoxin isolated from mussels, has been elucidated by total synthesis which also enriched its supplies. The degradatively derived fragments of this marine biotoxin, compounds 5 (EFGHI), 6 (FGHI), and 40 (ABCD), were matched with synthetic materials, thus confirming their structural identities. Based on this detective work, a new structure of azaspiracid-1 (i.e., 1) was proposed and constructed by total synthesis. The final strategy for the total synthesis of azaspiracid-1 featured a dithiane anion (C(21)-C(27) fragment) reacting with a pentafluorophenol ester (C(1)-C(20) fragment) followed by a Stille-type union of an advanced allylic acetate substrate (C(1)-C(27) fragment) with a vinyl stannane as the main coupling processes to assemble the carbon skeleton of the molecule. In addition to the total synthesis of azaspiracid-1 (1), the syntheses of its C(1)-C(20) epimer (2) and of several truncated analogues for biological investigations are described.     

Synthesis of an A-E gambieric acid subunit with use of a C-glycoside centered strategy

This paper describes our synthesis of the A-E subunit of gambieric acid (GA) in addition to the synthesis of the A-ring and the C-E tricycle. The use of an enol ether-olefin RCM strategy to couple the A and C-E subunits and, in the process, generate the B-ring is noteworthy.     

Synthesis of the ABCD fragment of gymnocin-B

A convergent synthesis of the ABCD fragment of gymnocin-B was accomplished. The tetracyclic ether ring system was synthesized by the construction of the BC ring system via the oxiranyl anion alkylation and ring expansion reaction, followed by the formation of the five-membered A-ring via a stereoselective radical cyclization reaction of a neopentyl-type iodide.     

Synthesis of the ABCD ring of gambierol

A fully functionalized ABCD ring moiety of gambierol, a marine polycyclic ether toxin, was synthesized by the use of the oxiranyl anion strategy and reductive cycloetherification of a beta,delta-dihydroxy ketone.     

Unified, radical-based approach for the synthesis of spiroketals

[reaction: see text] Functionalization of S-(3-chloro-2-oxo-propyl)-O-ethyl xanthate 1 by two consecutive xanthate transfer reactions, followed by spirocyclization of the resulting dihydroxy ketones, provides a flexible and highly convergent access to diversely substituted spiroketals, containing five-, six-, and seven-membered rings.