Identification of marneral synthase, which is critical for growth and development in Arabidopsis.

Plants produce structurally diverse triterpenoids, which are important for their life and survival. Most triterpenoids and sterols share a common biosynthetic intermediate, 2,3-oxidosqualene (OS), which is cyclized by 2,3-oxidosqualene cyclase (OSC). To investigate the role of an OSC, marneral synthase 1 (MRN1), in planta, we characterized a Arabidopsis mrn1 knock-out mutant displaying round-shaped leaves, late flowering, and delayed embryogenesis. Reduced growth of mrn1 was caused by inhibition of cell expansion and elongation. Marnerol, a reduced form of marneral, was detected in Arabidopsis overexpressing MRN1, but not in the wild type or mrn1. Alterations in the levels of sterols and triterpenols and defects in membrane integrity and permeability were observed in the mrn1. In addition, GUS expression, under the control of the MRN1 gene promoter, was specifically detected in shoot and root apical meristems, which are responsible for primary growth, and the mRNA expression of Arabidopsis clade II OSCs was preferentially observed in roots and siliques containing developing seeds. The eGFP:MRN1 was localized to the endoplasmic reticulum in tobacco protoplasts. Taken together, this report provides evidence that the unusual triterpenoid pathway via marneral synthase is important for the growth and development of Arabidopsis.

Diverging pathways to topologically complex polycyclic bis-acetals and their ring system interchange.

Carbinol-tethered octalin-diols (1), which differ only by the C11 configuration at the angular position, were transformed selectively to three types of structurally unrelated original scaffolds such as unsymmetrical octahydroanthracenes (5/7), furofuranes (6), or spirans (8/9) via a two-step protocol. The 11S* configuration ensures a C13-C4 Friedel-Crafts type C-C bonding (through an unprecedented oxidative cleavage-triggered domino process) while the 11R* configuration allows for a C13-C2 Marson-type Friedel-Crafts C-C bonding (through a nucleophilic acetal opening).

Competing domino processes: path-discriminating ability of epoxide stereochemistry at the angular position.

Structurally different products can be reached selectively from unsaturated vicinal bicyclic diols, which differ only by the epoxide configuration at the angular position. It is possible to modify the regiochemical outcome of the domino process in such a way as to create a different pathway, [4 + 2] versus [4 + 3 + 2], and control product distribution by using the configuration bias. No previous example of a domino variant of the [4 + 3 + 2] process appears to have been documented.

Total synthesis and structural confirmation of ent-galbanic acid and marneral.

By capitalizing on a highly selective Claisen rearrangement, ent-galbanic acid 1 and (+)-marneral 2 have been synthesized. The relative configurations of (+)- 1 and (+)- 2 were unambiguously established by X-ray crystallographic analysis of the precursors 11a and 20, with the absolute configuration ensuing from their derivation from R-pulegone. In this way, the controversial issue of the configuration of galbanic acid was unequivocally settled.

Microwave-accelerated competing domino processes: a tether-controlled dual pathway into high molecular complexity.

Bicyclic unsaturated diols undergo a path selective modular domino transformation upon subjection to Pb(OAc)4, the reaction being biased to the nature of the angular substituent. The magnitude of the linking chain and the nature of the angular substituent determine the reaction course. Methylene ether linkage acts as an autoremovable directing group (ring-retained domino product 5), whereas a propylene linkage switches the path toward the ring-expanded type 21 domino product. Reaction times were substantially reduced using microwave irradiation.

Enantioselective synthesis of iridal, the parent molecule of the iridal triterpenoid class.

The monocyclic triterpene iridal 1 (parent molecule) is synthesized by an approach that allows access for several representatives of the iridal family as well as diversely substituted analogues. The success of the proposed synthetic plan depends upon the effortless stereoselective establishment of the trans C10/C11 dimethyl relationship in B-ring moiety 7 using a domino-based methodology and the higly efficient Miyaura-Suzuki type sp3-sp2 segment coupling 7 and 8, respectively.

Exploring modular domino reactions: competing processes based on the nature of the angular substituent.

The octaline diol system 6 was found to undergo an interesting set of reactions upon treatment with PhI(OAc)2, leading, in a single synthetic operation, to complex oxygen heterocycles. Experimental evidence supports an intramolecular hetero[4 + 2 + 2] adduct that has heretofore never been observed, which completely dominates the hetero[4 + 2] path in several cases. The domino protocol can be biased one way or another depending on both the nature of the pi-system and the length of the methylene spacer at the angular position.

A domino-based approach toward stereodefined heavily functionalized cyclohexanes: synthesis of iridal's core structure.

A stereoselective synthesis of heavily functionalized six-membered ring subunits, which possess functionality at sites appropriate for further elaboration, is described. The cyclopentanone moiety of hydrindenediol is required to achieve total facial selectivity during the pre-domino installation of the second quaternary center, while oxidative cleavage is responsible for the ring-expanding rearrangement. A microwave-assisted version of the key domino transformation and a test of concept approach toward the iridal core structure are also presented.

Enantioselective total synthesis of 1-epi-pathylactone A.

[structure: see text]. The first enantioselective total synthesis of 1-epi-pathylactone A, 3, has been accomplished using a PhI(OAc)2-mediated domino reaction as a key step. No diastereomeric separation was required throughout the whole synthetic scheme presented in this paper. Comparison of 1H and 13C NMR spectral data of the synthetic product with the reported spectral data of natural pathylactone A, coupled with an X-ray crystallographic analysis, led to the conclusion that the C1 configuration in the original paper was erroneously ascribed to (R).

The domino chemistry approach to molecular complexity: competing domino processes modulated by the substitution pattern.

Oxidative cleavage with lead tetraacetate results in the synthesis of different oxygen heterocycles starting from the same unsaturated 1,2-diol of type I by tuning of the substitution pattern at the angular position. When this compound bears a functional substituent, such as an alkoxy, ester, alkenyl, or simply a hydrogen, more than one reaction pathway are in competition. The process allows for the selective formation of three different complex ring systems, by the appropriate choice of the angular substituent, leading to either a ring-expanded type 1, ring-retained type 2, or domino products 3.

An efficient one-pot approach to bridged bicyclic ring-systems through consecutive hetero-domino transformations: a mechanistic rationale and further rearrangements.

This article describes the design of olefin-generated/reagent-modulated consecutive hetero-domino reactions of 1,2-unsaturated bicyclic diols, which are potentially of great use, initiated by PhI(OAc)(2), continued by [Pb(OAc)(4)], and completed by use of a mild base (K(2)CO(3)). Inversion of a quaternary center has been achieved through a three-reaction sequence: a domino transformation followed by an m-CPBA-mediated Baeyer-Villiger oxidation and subsequent reductive lactone ring opening.

Lead tetraacetate mediated one-pot multistage transformations: theoretical studies on the diverging behavior in the Hajos-Parrish and Wieland-Miescher series.

A computational approach to the proposed mechanistic rationale of the lead tetraacetate mediated oxidative cleavage of selected unsaturated diols in the hydrindenediol (derived from the Hajos-Parrish ketone, abbreviated as HP) and octalindiol (derived from the Wieland-Miescher ketone, abbreviated as WM) series is presented. These two unexpected cascade-type transformations have been found to yield structurally different products despite the similarities in the starting compounds 1-HP and 1-WM, which differ only by the number of carbon atoms in the cycloalkane rings. The final product in the HP series is the complex ring-expanded molecule iii-6, while the final product in the WM series is the ring-expanded bisacetoxy diacetal 7. Calculations carried out at the B3LYP/6-31G level have revealed the fact that the transformations of i-6 to ii-6 and of i-7 to ii-7 are endothermic by 19.93 and 4.20 kcal/mol, respectively. The isomerization of compounds i to ii is more endothermic in the case of the HP series. Furthermore, calculations have shown the transformation of i to ii to be kinetically less favored in the HP series than in its analogue WM series. The activation barrier for the transformation of i-6 to ii-6 is calculated to be 22.09 kcal/mol, whereas the corresponding barrier in the WM series is 13.77 kcal/mol. The thermodynamic features of the reactions support the experimental findings as well: 7 is calculated to be more stable than iii-7, and iii-6 is more stable than 6, as expected. The diverging behavior in the mechanism of the interconversion of i to ii has been attributed to the stabilization of the positive charge by a carbonyl oxygen in ii-7 due to the flexibility of the seven-membered ring in contrast to the rigidity of the six-membered ring.

First synthesis of the antifungal oidiolactone C from trans-communic acid: cytotoxic and antimicrobial activity in podolactone-related compounds.

The synthesis of the fungicide oidiolactone C starting from diterpenic trans-communic acid was carried out with an overall yield of 11.7%. The key step in the process consists of a new bislactonization reaction catalyzed by Pd(II), which gives rise to the podolactone-type tetracyclic skeleton from a norlabdadienedioic acid. We also carried out a study of the structure-biological activity of different natural podolactones and their synthetic precursors. Thus, the highest cytotoxic activity was found in dienic dilactones with ether-type substitutions on C-17, whereas the closure of the gamma-lactone ring is not critical for presenting a maximal antimicrobial activity.