Nonenzymic Laboratory Cyclization of Squalene 2,3-Oxide

Tamelen, E. E. Van; Willet, Julious L.; Schwartz, Manfred; Nadeau, Ronn

doi:10.1021/ja00976a048

Cited by 79 publications

(46 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As there is indirect evidence [51] for the transient formation of a protolanosterol intermediate (Scheme 1) the chiral methyl group is envisaged as migrating with retention of configuration from C-14 to C-13 in this intermediate. However, the result can be equally well accommodated by the alternative mode of cyclisation of (3S)-2,3-oxidosqualene which has been proposed by van Tamelen et d. [14,52,53] in which the first intermediate is postulated to be a perhydrocyclopentanonapthalene carbonium ion that undergoes several rearrangements to form lanosterol in a way that is consistent with the detailed information [35] on the migration of the hydrogen and methyl groups. 'The details of this scheme are such that the migrations of the methyl groups are postulated to occur on a protolanosterol skeleton in which the positive charge is placed on C-13 following the completion of the two hydride migrations.…”

Section: Resultssupporting

confidence: 68%

Stereochemistry of a Methyl-Group Rearrangement during the Biosynthesis of Lanosterol

Phillips

Clifford

1976

Eur J Biochem

View full text Add to dashboard Cite

2. Each mevalonate was converted into cholesterol by a rat liver preparation. 3. Each cholesterol specimen was converted into androsta-l,4-diene-3,17-dione by incubation with Mycobacteriumphlei in the presencd of 2,2'-dipyridyl. Each specimen of androsta-l,4-diene-3,17-dione was converted into androsta-l,4-dien-3-one-l7-ethylene ketal.4. The samples of androsta-1,4-dien-3-one-17-ethylene ketal were each converted chemically into oestrones in which the methyl group at C-18 is the only carbon atom that originated from C-6 in mevalonolactone.5. The oestrone from (3RS)-[6-3H1 ,6-'4C]mevalonolactone was oxidised chemically to acetic acid which was converted into p-bromophenacyl acetate and the 3H/14C ratio was measured.6. There was no overall loss of tritium from the methyl group of acetic acid, as measured by determining the 3H/14C ratios of the p-bromophenacyl esters, when the synthetic and degradative procedures 1 -5 were tested with [3H,,2-'4C]acetic acid.7. The oestrones derived from the 6R and 6S-mevalonolactones were oxidised. The chiralities of the resulting acetates were determined by an established procedure whereby the acetates were converted into 2s-malates which were examined for loss of tritium on equilibration with fumarate hydratase.8. The oestrone from (3RS,6R)-[6-2Hl,6-3Hl,6-'4C]mevalonate gave acetic acid which was converted into 2s-malate that retained 68.6 % of its tritium after treatment with fumarate hydratase ; the configuration of this acetic acid was R. 9. The oestrone from (3RS,6S)-[6-2Hl,6-3Hl,6-'4C]mevalonate was oxidised to acetic acid which was converted into 2s-malate that retained 31.9 % of its tritium after treatment with fumarate hydratase; the configuration of this acetic acid was S. 30. There was no overall change in the configuration of a chiral methyl group between C-6 of mevalonate and C-18 of oestrone. It is concluded that the intramolecular migration of a chiral methyl group from C-15 in 2,3-oxidosqualene to C-13 in lanosterol is stereospecific and occurs with overall retention of configuration.The stereochemical synthesis and configurational assay of the chiral methyl group [1,2] have led to the elucidation of the substrate stereochemistry of many enzymic reactions. The chiral methyl has been used to study the stereochemistry of two types of biological [4,11]. The work described in this paper represents a novel use of the chiral methyl group to elucidate the stereochemistry

show abstract

Section: Resultssupporting

confidence: 68%

Stereochemistry of a Methyl-Group Rearrangement during the Biosynthesis of Lanosterol

Phillips

Clifford

1976

Eur J Biochem

View full text Add to dashboard Cite

show abstract

“…Pioneers in this area include Goldsmith [26] and van Tamelen [27] but perhaps the most significant contributions were made by Johnson. [28] Johnson et al spectacularly demonstrated the viability of a biomimetic polycyclisation approach to steroids with a landmark total synthesis of progesterone.…”

Section: One-component Domino Reactionsmentioning

confidence: 99%

Multi-Bond Forming Processes in Efficient Synthesis

Green¹,

Sherburn²

2013

Aust. J. Chem.

View full text Add to dashboard Cite

An increasing number of synthetic organic chemists are embracing the philosophy of efficiency. Herein we highlight multi-bond forming processes, which form two or more new covalent bonds in a single synthetic operation. Such processes, which have the ability to rapidly increase structural complexity, are preeminent in contemporary synthetic organic chemistry. In this short review we classify, analyse, and contrast contemporary multi-bond forming processes, frame these cutting edge contributions within a historical context, and speculate on likely future developments in the area.

show abstract

“…Support for this hypothesis can be found in the 1966 synthetic work of van Tamelen, who showed that cyclization of 5 followed by rearrangement to 86 could be accomplished using a simple (nonenzymatic) Lewis acid (Scheme 19). 105 The enzyme is believed to simply protect the intermediates in the cascade to lanosterol from premature quenching, perhaps by proton loss or nucleophilic attack by water.…”

Section: Site-directed Mutagenesismentioning

confidence: 99%