A formal total synthesis of (+/-)-enterolactone

A radical cyclization based methodology has been applied for the formal total synthesis of (+/-)-enterolactone (1), the first lignan isolated from human source. Bromoacetalization reaction of the cinnamyl alcohols 7 and 13 using ethyl vinyl ether and NBS, generated the bromoacetals 8 and 15. The 5-exo-trig radical cyclization reaction of the bromoacetals 8 and 15 with in situ generated catalytic tri-a-butyltin hydride and AIBN furnished a 3 : 2 diastereomeric mixture of the cyclic acetals 9 and 16. Sonochemically accelerated Jones oxidation of the cyclic acetals 9 and 16 yielded the gamma-butyrolactones 10 and 12 completing the formal total synthesis of (+/-)-enterolactone. Alternatively radical cyclization of the bromoacetate 17 furnished a 1 : 2 mixture of the lactone 10 and the reduced product 18.

Synthesis based on cyclohexadienes .22. Formal syntheses of patchouli alcohol and norpatchoulenol

The preparation of 6-endo-formyl-1,3,3-trimethylbicyclo[2.2.2]octan-2-one 7 and 6-endo-acetyl-1,3,3-trimethylbicyclo[2.2.2]octan-2-one 8, the two key intermediates for the synthesis of patchouli alcohol 1 and norpatchoulenol 2, is reported by a simple and short method from 2-methylbenzoic acid.

A short, formal synthesis of (+/-)-2-pupukeanone

A short approach to (+/-)-2-pupukeanone, starting from 2,6-dimethylcyclohexenone employing a combination of Michael-Michael reaction and an intramolecular rhodium carbenoid C-H insertion as key reactions, is described.

A ring closing metathesis based approach for the spiroannulation of cyclopentanes and cyclohexanes. Formal synthesis of (+/-)-acorones

An efficient ring closing metathesis (RCM.) reaction based approach was developed for the spiroannulation of cyclopentanes and cyclohexanes and its utility demonstrated in the formal synthesis of the spirosesquiterpenes acorones.

A convenient enantiospecific methodology for (-)-(1R,5S)-1,5-dimethylbicyclo[3.3.0]octa-2,7-dione: A formal total synthesis of (-)-ceratopicanol

An enantiospecific formal total synthesis of (-)-ceratopicanol starting from the readily and abundantly available monoterpene (R)-limonene is described. A combination of Claisen rearrangement-intramolecular diazo-ketone cyclopropanation-regiospecific reductive cyclopropane cleavage reactions are employed for the stereo- and regiospecific generation of the two vicinal ring junction quaternary carbon atoms.

Synthesis based on cyclohexadienes Part 36: an efficient methodology for the construction of spiro[4.5]decanes: a formal synthesis of acorone

An efficient strategy for the contruction of spiro[4.5] decanes is described and involves a bridgehead substitution of a methoxyl group by a methyl group followed by an oxidative cleavage of the tricyclo[5.2.2.0(1,5)] undecane 25 to produce the spiro[4.5] decanes 31 & 32 which are intermediates in the synthesis of acorone. A novel one-pot conversion of alpha-methoxy carboxylic acid to alpha-methyl carboxylic acid is described.

Enantioselective Formal Synthesis of Palmerolide A

Enantioselective formal synthesis of macrolactone palmerolide A, a polyketide marine natural product, is described. Key strategies in the synthesis include the oxidative furan ring-opening of a chiral furyl carbinol for the installation of the 1,4-dienol core and a Jung nonaldol-aldol reaction for the dienamide core.

Towards formal verification of analog mixed signal designs using SPICE circuit simulation traces

An extension to a formal verification approach of hybrid systems is proposed to verify analog and mixed signal (AMS) designs. AMS designs can be formally modeled as hybrid systems and therefore lend themselves to the formal analysis and verification techniques applied to hybrid systems. The proposed approach employs simulation traces obtained from an actual design implementation of AMS circuit blocks (for example, in the form of SPICE netlists) to carry out formal analysis and verification. This enables the same platform used for formally validating an abstract model of an AMS design, to be also used for validating its different refinements and design implementation; thereby, providing a simple route to formal verification at different levels of implementation. The feasibility of the proposed approach is demonstrated with a case study based on a tunnel diode oscillator. Since the device characteristic of a tunnel diode is highly non-linear with a negative resistance region, dynamic behavior of circuits in which it is employed as an element is difficult to model, analyze and verify within a general hybrid system formal verification tool. In the case study presented the formal model and the proposed computational techniques have been incorporated into CheckMate, a formal verification tool based on MATLAB and Simulink-Stateflow Framework from MathWorks.

An Enantiospecific Formal Total Synthesis of the 5-8-5 Tricyclic Diterpene ent-Fusicoauritone

An enantiospecific formal total synthesis of the 5-8-5 tricyclic diterpene fusicoauritone has been accomplished, starting from 5-isopropyl-2-methylcyclopent-1-enemethanol [available in three steps from (R)-dihydrolimonene] employing two ring-closing-metathesis reactions for the construction of the eight- and five-membered rings.

Formal Synthesis of Actin Binding Macrolide Rhizopodin

Formal synthesis, of an actin binding macrolide rhizopodin was achieved in 19 longest linear steps. The key features of the synthesis include a stereoselective Mukaiyama aldol reaction, dual role of a Nagao auxiliary (first, as a chiral auxiliary of choice for installing hydroxy centers and, later, as an acylating agent to form an amide bond with an amino alcohol), late stage oxazole formation, and Stille coupling reactions.

Unexpected mechanism for formal 2+2] cycloadditions of metallacyclocumulenes

The formation of radialene complex 6M proceeds through a three-membered metallacyclopropene complex 7M, contrary to the prevailing notion of simple dimerization of metallacyclocumulene 1M. The 1M-7M equilibrium, which is predominantly governed by the size-dependent ligand binding of the metal atoms, plays a decisive role in the chemistry of Cp2M-ligand complexes. This size dependency is further fine-tuned by the substituents on the substrates and helps in exploiting these classes of metallacycles to generate new chemistry.

Enantiospecific Formal Total Synthesis of Iriomoteolide 3a

A formal total synthesis of the marine macrolide iriomoteolide3a is described. Salient features of the synthesis include the elaboration of a -keto phosphonate derived from D-(-)-tartaric acid and the extension of a chiral butyrolactone derived from L-glutamic acid. Ring-closing metathesis is employed to construct the macrolactone core of the natural product.

Using formal reasoning on a model of tasks for FreeRTOS

FreeRTOS is an open-source real-time microkernel that has a wide community of users. We present the formal specification of the behaviour of the task part of FreeRTOS that deals with the creation, management, and scheduling of tasks using priority-based preemption. Our model is written in the Z notation, and we verify its consistency using the Z/Eves theorem prover. This includes a precise statement of the preconditions for all API commands. This task model forms the basis for three dimensions of further work: (a) the modelling of the rest of the behaviour of queues, time, mutex, and interrupts in FreeRTOS; (b) refinement of the models to code to produce a verified implementation; and (c) extension of the behaviour of FreeRTOS to multi-core architectures. We propose all three dimensions as benchmark challenge problems for Hoare's Verified Software Initiative.